dos_oct_2013

Delhi
Ophthalmological
Society

Contents

5 Editorial Miscellaneous

Experts’ Corner 55 Ophthalmic Lens Dispensing

11 Keratoprosthesis Ashima Bhargava, Pooja Singh


Evolution
Theme: Ocular Surface Disorder
63 Evolution of Ocular Surface Transplantation
17 Cell Based Therapy for Ocular Surface
Reconstruction Tarun Arora
Rajat Jain, Shraddha Sureka, Anthony Vipin
Das, Sayan Basu, Virender S. Sangwan PG Corner
31 Mucous Membrane Graft
Vishnukant Ghonsikar, Neelam Pushker, 69 Ocular Chemical Injuries
M.S. Bajaj
Dry Eye Diagnosis and Management Sandeep Gupta
Revisited
35 Rohit Shetty Monthly Meeting Corner
Allergic Conjunctivitis– A Review
Bithi Chowdhury 73 NSAIDS – A Double Edge Sword

41 Ashish Khindria, Jayeeta Bose

Tear Sheet

Diagnostics 87 Ocular Surface Disease Management

49 Sana Ilyas Tinwala

Corneal Topography
Aditi Manudhane, Ritu Arora, J.L.Goyal,
Parul Jain, Gaurav Goyal

www. dosonline.org l 3

“The over-all point is that new technology will not necessarily
replace old technology, but it will date it. Eventually, it will
replace it. But it’s like people who had black-and-white TVs when
color came out. They eventually decided whether or not the new
technology was worth the investment.”

-Steve Jobs

Respected Seniors & Dear Friends,
Winter conference is round the corner and excitement is in the air. A fresh
venue for this conference is the first of the many exciting changes that the
members felt was imminent. And I guess variety is the spice of our life.
Change keeps our blood flowing, our heart pumping and mood elevated. If
we don’t change, we don’t grow. If we don’t grow, we aren’t really living.
Manekshaw Centre is a state of the art Centre with its royal designing and
pleasant environment that will give the right atmosphere for inculcation of
new ideas.
Various neoteric ideologies that were in research phase in previous meetings
have now started to find applications in clinical spheres. Newer innovations
that spell bounded us in the foregoing meetings will try to prove their mettle in
long-term results. True to the theme of this year’s conference, “OphthaNeo:
Evolving Trendz”, it will showcase some great innovators, leaders and
visionaries discussing the way the field of ophthalmology will evolve in the
coming years.
Technological innovation is indeed important to scientific growth and the
enhancement of human possibilities. And for good ideas and true innovation,
you need human interaction, conflict, argument and debates. And I hope that
the winter conference will be the perfect ground for same, when hundreds of
participants will confluence on 30th November to 1st December. Ultimately
it is innovation that distinguishes between a leader and a follower.
Sincerely Yours

Rajesh Sinha
Secretary,
Delhi Ophthalmological Society

www. dosonline.org l 5

Guest Editorial Editorial Board

Globalization of the DOS EEdditiotroiarl-iBno-carhdief
Boston Keratoprosthesis
Rajesh Sinha
Roughly 10 million persons are corneal blind, world-wide. Many
of them are children, and the great majority are poor. The Boston Executive Editor
keratoprosthesis, invented by Dr. Claes H. Dohlman, and approved
for marketing by the US Food & Drug Administration in 1992, is Sandeep Gupta
indicated for those patients with corneal blindness in whom corneal Digvijay Singh
transplantation is unlikely to succeed. There are two designs. The
Boston keratoprosthesis type I, assembled in nut-and-bolt fashion Editorial Board
in a donor cornea and then sutured in the eye as in a standard
penetrating keratoplasty, is intended for patients with a normal Ritika Sachdev
tear film and eyelid function. The Boston keratoprosthesis type II, has an anterior extension of its optic to Ramendra Bakshi
protrude between surgically closed eyelids, and is used in patients with severe dry eye and ocular surface Pooja Bandivadekar
keratinization, such as mucous membrane pemphigoid and other cicatricial conjunctival disorders. Both
designs utilize an optical component made of polymethyl methacrylate (PMMA), and a backplate, made of Sana Tinwala
either PMMA or titanium. Srilathaa G.
The Boston keratoprosthesis can restore essentially normal vision to patients after multiply failed corneal Dewang Angmo
grafts, but also in those with scarred, vascularized corneas after infection and trauma, including chemical Vishnukant Ghonsikar
burns, in inherited disorders such as aniridic keratopathy, and in autoimmune disorders, including Sjögren’s
syndrome, mucous membrane pemphigoid and Steven’s Johnson syndrome. Clinical outcomes with Ravi B.
the device, including visual acuity and device retention, have improved markedly in the last decade, Shorya Vardhan Azad
with advances largely due to changes in device design and postoperative care. For example, holes in
the previously solid backplate dramatically reduced the incidence of sterile keratolysis, as did institution Tarun Arora
of full time contact lens wear over the device. Topical antibiotics, typically two antibiotics with different Anirudh Singh
mechanisms of action to reduce the likelihood of inducing antibiotic resistance, for example vancomycin and Vinod Agarwal
a fluoroquinolone, or polymixin B and trimethoprim, have dramatically lowered the risk of endophthalmitis
after device implantation. Neha Goel
However, serious complications remain that complicate use of the device. Glaucoma remains a Parul Jain
frequent complication of keratoprosthesis implantation and eventually robs many otherwise successful Reetika Sharma
keratoprosthesis recipients of their restored vision. Although penetrating keratoplasty itself is also
associated with both worsening of pre-existing glaucoma and new onset of glaucoma, keratoprosthesis Rebika
recipients are particularly vulnerable because rigidity of the keratoprosthesis backplate prevents accurate
tonometry. Keratoprosthesis surgeons and their glaucoma specialist colleagues are left with only tactile DOS Correspondents
(fingertip) estimation of intraocular pressures. It is altogether too easy to apply wishful thinking to such
estimations; hoping and/or praying the eye pressure is not as high as it feels often leads to permanent, Supriya Arora
unrecoverable vision loss for the patient. Prateek Kakkar
Infection represents a second serious complication of particular importance. Because the Boston Ruchita Falera
keratoprosthesis bridges the external environment and the inner eye, infections of the corneal tissue Ruchir Tewari
surrounding the device are not trivial and can lead quickly to endophthalmitis and loss of the eye. Although Manthan Chaniyara
daily, topical, double antibiotic therapy for life appears to dramatically reduce the risk of bacterial infection Vineet Sehgal
after keratoprosthesis implantation, it may increase the risk of fungal overgrowth and infection around
the device, potentially leading to endophthalmitis and loss of useful vision. Therefore, keratoprosthesis Nasreen
recipients are at risk of bacterial keratitis and endophthalmitis after just a few days without their topical Ravish Kinkhabwala
antibiotics, and ironically, for fungal keratitis and endophthalmitis when they use those drops unfailingly.
Fungal infection may be a particular danger in those patients with autoimmune disorders, those with a Pulak Agarwal
neurotrophic cornea, and those in warm, humid climates where molds account for the majority of corneal Akshay Tayade
ulcers in the general population.
International growth in use of the Boston keratoprosthesis now outpaces the USA and Europe. Many of the Advisory Board
most needy potential recipients lack sufficient economic resources to maintain topical antibiotics and contact
lens use, and may have difficulties with transportation to postoperative appointments. Judicious patient R.V. Azad
selection, rigorous adherence to topical medications, ready access to eye care providers with experience in Y.R. Sharma
identifying complications of keratoprosthesis surgery and postoperative examinations at frequent intervals,
are all essential ingredients for success after implantation of the Boston keratoprosthesis, regardless of J.S. Titiyal
where the patient lives and receives their surgery. A.K. Grover
Lalit Verma
Dr. James Chodosh MD, MPH Rajendra Khanna
Associate Director, Cornea and Refractive Surgery Mahipal S. Sachdev
Massachusetts Eye and Ear Infirmary Atul Kumar
David Glendenning Cogan Professor of Ophthalmology B.P. Guliani
Harvard Medical School Harbansh Lal
Boston, Massachusetts V.P. Gupta
Ramanjit Sihota
Cover Designed by: Aman Dua Praveen Malik
Layout Designed by: Mahender Abhishek Dagar
Published by Dr. Rajesh Sinha for Delhi Ophthalmological Society P.K. Sahu
Printers: K.D. Printo Graphics, 2/20, 1st Floor, D.D.A. Market J.K.S. Parihar
Complex, Near SBI, Dr. Ambedkar Nagar, New Delhi,
Email: [email protected] B. Ghosh
Tanuj Dada
Amit Khosla
Namrata Sharma
Sanjeev Gupta
Umang Mathur
J.S. Bhalla
Rohit Saxena
Bhavna Chawla
Manisha Agarwal

wwwwww. d. odsoosnonlilnine.eo.rogrgll 7

World Sight Day

Saturday, 12th October, 2013

Delhi Ophthalmological Society, Dr. R.P. Centre,
A.I.I.M.S. & C.R.P.F., Bavana, Delhi

A Comprehensive Eye Screening Camp was conducted on 12.10.2013 on the occasion of “World
Sight Day” by DOS, Dr. R.P. Centre & CRPF at CRPF Camp Bawana, New Delhi in which 590 patients
were examined. Out of these, 52 patients were identified for cataract surgery and referred to Dr. R.P.
Centre for surgery. A total of 415 refractions were conducted in the camp and 408 spectacles were
prescribed and dispensed.

The school vision screening programme was also conducted; six schools were covered in this
programme; 838 children were screened and 57 refractions were conducted and 55 spectacles were
prescribed and issued.

Experts’ Corner

Keratoprosthesis

The history of Keratoprosthesis (KPRO) development dates back to the 18th century. The modern James Chodosh
era, in which various forms of polymethylmethacrylate (PMMA) are used, began in the 1950s. While Quresh B. Maskati
KPro remains a procedure to be considered only in instances of poor prognosis keratoplasty, the Radhika Tandon
improvements in design, surgical technique, and postoperative care have resulted in a dramatic
improvement in results over the past quarter century. Indu Singh
The EXPERT’S CORNER on Keratoprosthesis in this issue, presents the views of a panel of experts with Geetha Iyer
wide experience in the aforementioned subject. The development over the years in the technique and
design of Keratoprosthesis, along with the peri-operative problems faced and their management, are
discussed at length by Dr. Sana Tinwala with Dr. James Chodosh, Dr. Quresh Maskati, Dr. Radhika
Tandon, Dr. Indu Singh and Dr. Geetha Iyer.

Dr. James Chodosh (JC): MD, MPH; David G. Cogan Professor of Ophthalmology,
Massachusetts Eye and Ear Infirmary, Howe Laboratory, Harvard Medical School, Boston, MA
Dr. Quresh B. Maskati (QBM): MS, DOMS, FCPS, FICS; Hon. Ophthalmic Surgeon: Saifee
Hospital, Mumbai, Hon. Ophthalmic Surgeon: Habib Hospital, Mumbal, Hon. Ophthalmic
Surgeon: Hinduja Hospital (Khar), Mumbai, India
Dr. Radhika Tandon (RT): MD, DNB, FRCOphth, FRCSEd; Professor of Ophthalmology,
Cornea and Refractive Surgery Unit and Officer–in-charge National Eyebank, Dr. Rajendra
Prasad Center for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi,
India
Dr. Indu Singh (IS): MS, Consultant Ophthalmologist, Dr. Daljit Singh Eye Hospital, Amritsar,
India.
Dr. Geetha Iyer (GI): FRCS Senior Consultant, C.J. Shah Cornea Services, Dr. G. Sitalakshmi
Memorial Clinic for Ocular Surface Disorders, Sankara Nethralaya, Chennai, INDIA
Dr. Sana Ilyas Tinwala (SIT): MD, DNB; Senior Resident, Cornea, Cataract and Refractive
Surgery Services, Dr. Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of
Medical Sciences, New Delhi, India

SIT: Who, according to you, are suitable candidates for keratoprosthesis? Your guidelines
for patient selection based on your clinical experience.

JC: Keratoprosthesis implantation is indicated in any patient with corneal blindness when
traditional keratoplasty, whether full thickness or lamellar, is likely to fail.

QBM: Those who have a functioning posterior segment, with no or controlled glaucoma,
with multiple failed grafts or candidates unsuitable for grafts. For the Boston Kpro, they must in
addition have a good eyelid action and adequate tears, with no keratinisation of the cornea and no
history of corneal melts.

For the Pintucci Bio-Integratable Kpro we can even help those with bone-dry eyes with
complete corneal keratinisation.

RT: Patients with bilateral blindness or severe visual impairment due to end stage corneal
disease with some visual potential and not suitable for routine keratoplasty.

IS: A suitable candidate for Kpro is the one in whom we cannot hope to try any other treatment

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Experts’ Corner

with better outcome. For example penetrating keratoplasty, SIT: Any modifications from your side in the described
optical iridectomy etc. technique of keratoprosthesis surgery?

The guidelines for patient selection are: Corneal JC: My technical approach is fairly standard, except I
blindness with good perception and projection of light and pay a lot of attention to proper corneal wound closure in order
normal B Scan. The cornea should be strong enough to hold to minimize formation of retroprosthetic membranes.
the Kpro In case of staphylomatous or very thin cornea we can
do para limbal Kpro. QBM: The Boston Kpro is done by me in the standard
way, except that I only use a 7mm back-plate. The latest version
GI: Patients with bilateral visual handicap due to corneal manufactured by Aurolab is also good. For the Pintucci, as
problem with a high risk of graft failure with conventional mentioned earlier, we have made some modifications in the
keratoplasty would be the ideal candidate. With this definition original design.
the ideal patient would be one with multiple failed grafts
especially for Boston Type 1 keratoprosthesis. RT: In very young patients in the age range 18 to 30
years we do extracapsular cataract extraction (ECCE) instead
However being a tertiary referral center our indications of intracapsular cataract extraction (ICCE).
have been primarily Stevens Johnson Syndrome (SJS) and
chemical injury. IS: Champagne cork Kpro relies for its support on two
types of fixations. Local fixation is with 100 microns steel
It is important to understand that K-Pros are the last resort sutures on to the cornea and distant fixation is also with 100
and you have exhausted all other options prior to performing microns steel sutures with the healthy sclera. Our aim should
the K-Pro procedures. At the same time, it is important to keep be to fixate it to the eye in the manner that it does not have
in mind the impact of the prior intraocular procedures on the micro movements when the eye moves. The pressure inside
outcome of the K-Pro surgeries. The broad guidelines would the eye and the pressure of these wires should be same. The
therefore be: sutures should be equidistant.

1) Bilateral visual handicap We also carry out para limbal fixation of this Kpro in the
2) End stage ocular surface disorder same way as we fix it on cornea.
3) Patients’ willingness to come for regular follow-ups
4) Those with realistic expectations GI: The technique of the Boston K-Pro surgery is as has
SIT: What type of keratoprosthesis do you commonly been described in the literature. MOOKP surgery has been
use in your clinical practice? classically described as being performed in 2 stages as per
JC: I use the Boston keratoprosthesis. the Rome-Vienna protocol. However, we prefer to do it in 3
QBM: The Pintucci Bio-Integratable K pro since 1997 stages. In the first stage, we prepare the eye and this includes
(85 cases); a modification we call the Chawan-Maskati-Pintucci intracapsular cataract surgery, iris removal and limited anterior
Kpro (or CMP Kpro) since early 2013 (2 cases) and the Boston vitrectomy with penetrating keratoplasty if indicated. During
Kpro since early 2009 (approx 12 cases). this stage we assess the fundus which gives us an idea regarding
RT: Modified osteo odonto Keratoprosthesis (MOOKP) the visual potential of the eye especially with respect to the
for patients over 18 years of age with end stage SJS with optic nerve status. This also reduces the surgical time during
severe keratinization of ocular surface and ‘0’ Schirmers’s not the 2nd stage of the MOOKP procedure when the lamina is
amenable to other ocular surface reconstructive procedures, in implanted in the eye.
patients who have a suitable canine tooth.
Boston Keratoprosthesis or equivalent devices such as SIT: Do you have any experience with keratoprosthesis
Auro or Lucia for patients without inflammatory eye diseases in the pediatric population?
and a wet blinking eye for example heavily vascularized
corneas with repeated failed grafts. JC: I am very selective when considering keratoprosthesis
IS: I use Champagne cork or Singh Worst Kpro in my in pediatric patients. The Boston keratoprosthesis can rescue
clinical practice. life-long vision for the right patient, but without excellent
compliance and follow up, patients may develop severe
GI: We have been doing the MOOKP at our centre infection and lose their eye. On the other hand, it is much
since 2003 and till date have done close to 90 procedures. We easier to prevent amblyopia with a Boston keratoprosthesis
started the Boston type 1 keratoprosthesis in 2007 and till date than with keratoplasty because there is no astigmatism with
have done 50 procedures. the keratoprosthesis.

MOOKP and Boston Keratoprosthesis are equally QBM: Yes, the Pintucci has been done by me in children
advised at our center with the choice of the Keratoprosthesis as young as 7 years of age as well.
depending on the indication, moistness of the eye, lid
condition and state of dental hygiene. RT: No.
IS: Yes. I have done 10 Kpro in children less than
15 years. This procedure has best results if the blindness is
recent. In case of congenital problems with opaque cornea,
the amblyopia is so deep that the child never appreciates the
images he sees. In very small children(less than 5 years) I don’t
advocate performing this procedure.

12 l DOS Times - Vol. 19, No. 4 October, 2013

Experts’ Corner

GI: We have done the Boston type 1 keratoprosthesis as other prosthesis. So in my opinion the best results are the
surgery in 2 pediatric patients. One was for a failed graft in results of good surgery.
the case of sclerocornea with a follow up of close to 3 years
now and doing well. The other was for congenital anterior GI: Firstly we would like to stress here that the
staphyloma with the other eye being anophthalmic. However indications for the 2 types of Kpros are basically different with
this eye developed a carrier melt and retroprosthetic membrane a very minimal overlap.
formation which required a repeat Keratoprosthesis along with
membranectomy. Boston Keratoprosthesis type 1 is an option for eyes
with adequate tears, good blink, no exposure and preferably
SIT: What are the outcomes of Boston K-pro in your without an underlying systemic immune condition like Stevens
setting? Johnson syndrome or ocular cicatrical pemphigoid (OCP).
Meaning it is a good option for failed grafts or chemical injuries
JC: When one considers that most patients I operate on with limbal stem cell deficiency but well-formed fornices in an
are blind with no other surgical or medical alternative, the adequately wet eye.
outcomes are excellent. Pre-existing glaucoma remains the
major impediment to visual improvement of patients in my MOOKP is an option in eyes with severe ocular surface
practice. damage associated with dryness and/or keratinization usually
noted in patients with an underlying systemic immune
QBM: Excellent, provided we have been choosy in condition like SJS or OCP. One of the main pre-requisites
patient selection. for a successful outcome of the MOOKP procedure is a good
dental hygiene and this has to be ascertained preoperatively in
RT: 80% anatomical retention, 100 % attained full consultation with the oro maxillo facial surgeon.
visual potential, 100% retained vision longer than all previous
corneal grafts. Retroprosthetic membrane occurs in over 60 % MOOKP can also be performed in eyes where a Boston
of cases, but is less with the Lucia. type 1 K-Pro is primarily indicated however considering the
challenging nature of the MOOKP surgery and the need for a
IS: I don’t have experience with Boston Kpro. multi-disciplinary approach, the Boston Type 1 K-Pro can be
GI: Our retention rate over the last 6 years has been performed in these eyes if the patient is willing for the postop
close to 80% and a best corrected visual acuity of better than care and regular follow-ups. In patients with poor dental
20/200 was achieved in close to 70% of the patients. hygiene that precludes performing the MOOKP surgery, other
SIT: While keratoprostheses are the last resort options such as the Tibial bone or Pintucci K-pro might be
in patients with corneal blindness, Can we consider required for visual rehabilitation.
osteodontokeratoprosthesis (OOKP) as the last resort
amongst keratoprostheses? Kindly give us a brief overview SIT: What is your success rate with keratoprosthesis?
of your experience with the same? What is the patient acceptance rate of the procedure in
JC: I prefer to use the Boston keratoprosthesis type II terms of satisfaction and quality of life?
in patients who are in need of a “last resort”, typically those
with end stage cicatricial conjunctivitis and ocular surface JC: Success can mean many things. My definition is
keratinization. The type II device has very similar outcomes whether the life of the patient is improved by the device. By
to OOKP, when one compares those outcomes by diagnostic that definition, keratoprosthesis implantation has a near 100%
category. The advantages of the type II device are less operating success rate, at least in the short and intermediate time frames
time and better cosmesis. But both techniques are evolving, (several years). In the longer term (decades), postoperative
and perhaps one day will merge into a single method for complications including infection and glaucoma remain
treating the cicatricial corneal blind. significant obstacles to retention of quality vision for many
patients.
QBM: The Pintucci and the MOOKP have similar
indications. The Pintucci is easier to perform, can be done in QBM: My success rate with the Pintucci is around 65%
a private set-up, does not need healthy teeth, therefore can be overall and around 50% if you only consider SJS patients. The
done for children and does not need a dentist or serial MRIs success rate with the Boston Kpro is around 80%.
at regular intervals to check the health of the implanted tooth.
RT: Success rate for improvement in vision was 100%
RT: Agreed. Cosmesis is a problem. Due to chronic with Boston KPro and 80% with MOOKP. The latter was due
inflammatory nature of SJS, reabsorption of ODAL after 5 years to one patient having a chronic shallow retinal detachment
is another problem. which was missed pre-operatively. Patients’ quality of life by
informal assessment improved with gaining ambulatory vision
IS: I have done just one case of OOKP. The vision of and coming out of the World Health Organisation (WHO)
that patient lasted for one year. I have seen and managed the category of blindness.
complications of OOKP done elsewhere. I have seen extrusion,
infection, retroprosthetic membrane and dislocation of this IS: I believe if we can make a patient ambulatory in
Kpro. If the surgery of this Kpro is perfect and there are no terms of vision, it will be considered successful. 90% of my
micro movements, the longevity of vision increases. In case patients have ambulatory vision for one year. They are satisfied
of complications they also have to be managed the same way and at least 60% of them have very good quality of life. The

www. dosonline.org l 13

Experts’ Corner

problem my patients face is that the corneas have multiple trickling into the vitreous cavity, or a decentered central
other problems. They can develop recurrent corneal ulcers or opening in the carrier graft.
leakages from thin corneas. In order to avoid that I have started
using buccal mucosal graft on these eyes. Post operatively retroprosthetic membrane, glaucoma,
infection, carrier melts have been noted with Boston
GI: Success rate depends on the type of keratoprosthesis, Keratoprosthesis.
the indication for which the K-Pro has been performed and
the presence of co-morbid conditions, of prime concern The intraoperative complications in MOOKP include
being glaucoma. It is extremely important to reiterate here the blood loss during harvesting the tooth, inadvertent entry
importance of the preoperative counseling for these patients into the maxillary sinus and decentered corneal opening
stressing upon the need for regular follow-ups, postoperative during stage 2 of the procedure. The risk of suprachoroidal
care, and the cosmetic outcome especially for the MOOKP hemorrhage exists during the preparatory stage as well the 2nd
procedure. stage. Postoperative complications include glaucoma, lamina
resorption and endophthalmitis.
Our retention rate for the MOOKP procedure over the
last 10 years has been close to 75% with a BCVA of better SIT: Considering the high rate of complications and
of 20/200 in more than 60% of patients. Broadly speaking, meticulous post-operative care required, what is the
the patients’ acceptance is reasonably good and we have routine post-operative follow-up regime for your patients?
had patients resuming their studies and joining public sector
undertakings after these sight restorative procedures. JC: Really, the most important point to make about
postoperative complications is to choose surgical candidates
SIT: What are the commonly seen complications carefully. Then, frequent follow up visits with repeated
intra-operatively and post-operatively? reminding about the absolute necessity to continue
topical antibiotics is the next most important aspect of
JC: Intraoperative complications with keratoprosthesis good postoperative care. My postoperative regimen in
surgery are the same as for keratoplasty and not difficult to keratoprosthesis patients after allograft rejection is once daily
manage for an experienced corneal surgeon. Postoperatively, topical antibiotic, often trimethoprim/polymixin B, and in
keratoprosthesis complications are now very well known, some cases, once daily corticosteroid. I generally try to stop
including infection, glaucoma, retinal detachment, sterile the latter, within the first 6 months after surgery. I may see such
vitritis, and retroprosthetic membrane. Those specific to patients in clinic every 3-6 months. In contrast, keratoprosthesis
keratoprosthesis are retroprosthetic membrane, sterile vitritis, implantation in patients with auto-immune disorders requires
and infections around the keratoprosthesis stem that if much more intensive follow up care. I examine my Stevens
unrecognized or delayed in treatment, can lead to infectious Johnson patients with keratoprosthesis every two months, and
endophthalmitis and loss of the eye. use twice daily fluoroquinolone and vancomycin drops.

QBM: Too many to list here. Suffice it to say that QBM: For the Pintucci Kpro, they are weaned off topical
there is hardly any one of my 85 Pintucci patients who did steroids and antibiotics about 3 months after the second stage
not have some minor or major complication, including 3 and maintained on lubricants. The Boston Kpro patients have
endophthalmitis and 8 retinal detachments (all successfully to change their large diameter scleral bandage lenses every 2
operated and retina flattened) I also have the world’s only months and be on topical antibiotics for life.
series of dropped Kpros (3 cases) in the vitreous. For the Boston
Kpro, glaucoma and retroprosthetic membrane and infections RT: MOOKP- monthly follow up till 6 months, them
are the commonly seen complications. 2 monthly till 1 year and 3-6 monthly thereafter, lifelong
monitoring for visual acuity, healthy mucous membrane,
RT: MOOKP- intraoperatively vitreous hemorrhage, stability and cleanliness of surface of optic, intraocular presure
fracture of ODAL and poor visibility from excessive mucosal (IOP) assessed by digital palpation, fundus evaluation.
bleeding, expulsive hemorrhage. Post-operatively, mucous
membrane overgrowth, ulceration, necrosis, absorption of Boston KPro- monthly follow-up till 6 months, then 2
ODAL, extrusion of ODAL, endophthalmitis, retroprosthetic monthly lifelong.
membrane, retinal detachment, chronic glaucoma.
IS: I like to see my patients very often. I tell them to visit
Boston KPro- fracture during assembly, hemorrhage me at least once in two months and in case of a complication
from corneal vesels tracking into vitreous cavity, expulsive or decrease in vision, they have to report immediately.
hemorrhage, choroidal detachment. Post-operatively,
instability of BCL, sterile corneal melt, infectious keratitis, GI: With respect to the MOOKP the post op care is
endophthalmitis, secondary glaucoma, retroprosthetic minimal with yearly checkups including visual field spiral CT
membrane. scan to assess the lamina dimension. Postoperative medications
include topical antibiotic ointment and lubricant drops and
IS: I have very few intra-operative complications after systemic acetazolamide in case of glaucoma. Postoperative care
more than a 1200 of these procedures. Post operatively these following Boston type-1 kpro is more stringent. We routinely
eyes can develop leakage, retroprosthetic membrane, corneal use prophylactic antibiotics in the form of vancomycin 14mg/
ulcers and very rarely extrusion or endophthalmitis. ml 2/day and 4th generation fluroquinolone 2/day for a long
period. The bandage contact lens (BCL) is changed once every
GI: With respect to the Boston Keratoprosthesis the 3 months and patients are required to report back for follow up
common intraoperative complication would be hemorrhage once every 3 months indefinitely.

14 l DOS Times - Vol. 19, No. 4 October, 2013

Experts’ Corner

SIT: What is the rate of re-surgeries in your patients? weaker sections of society and have to run around trusts and
JC: This depends entirely on the preoperative diagnosis. donors to scrape up the money to pay for the Kpros.
Reoperation is rare in allograft rejection patients, and common
in autoimmune diseases. RT: Considering the procedures give visual rehabilitation
QBM: The Pintucci is a surgery of last resort. If it fails, for a finite period of time, typically 2-5 years, rarely 10-15 years,
no more surgery is possible. For the Boston Kpro once can and are very effort intensive for chronic use of medications
always change it if there is infection of the donor graft. and mandatory follow up, they should only be offered for end
RT: 5%. stage disease in patients for whom there is no other option.
IS: I would like to call this “management of Informed consent should include discussion of complications,
complications”. Almost 60% of my patients have to come cosmesis, expenses incurred in follow up visits and risks of
for re-evaluation of their eyes. There are instances when severe irreversible sight threatening complications.
conjunctiva grows on Kpro, so we have to create an opening.
Sometimes we clean the surface of Kpro. Some patients need IS: Champagne cork Kpro is easily affordable and since
refixation of Kpro if it is slightly loose. we never charge the patients for revisits, our patients do not
GI: Surgical intervention following kpro surgeries have any problem.
can be for multiple indications. Re-surgeries meaning re-
keratoprosthesis procedure was required in 10 % of the GI: Keratoprostheses surgeries are sight restorative
MOOKP patients to salvage or replace the lamina over a 10 procedures in patients who are bilaterally visually
year period and same has been 7 % for the Boston K-Pro over handicapped. In the event of an uneventful surgical procedure,
a 5 year follow up period. these patients recover a good visual outcome and can get back
SIT: AlphaCor is another keratoprosthesis that has to a relatively normal course of life. Most of these patients
shown good results in some hands- we would like to know are young individuals and are otherwise socio economically
your views on the same. dependent on others. The cost of kpro surgery to the patient
JC: I do not use the AlphaCor any longer. includes the surgical charges with the cost for the implant and
QBM: AlphaCor has been given up world wide as its the cost of the postoperative care and follow-ups. There have
usefulness was very limited. been studies to determine the cost effectiveness of the surgeries
RT: It is expensive and contraindicated in those with for both MOOKP and Boston type 1 kpro. These studies have
Herpes Simplex keratitis. shown after taking into consideration various parameters that
IS: I don’t have experience with it. these procedures are definitely cost effective.
GI: We do not have experience with the same.
SIT: We would like to know your views on the SIT: Any other innovative design from your side?
economics of these procedures- how cost-effective are JC: The titanium back plate was recently FDA approved
these surgeries considering the complication rate and the for use in the Boston keratoprosthesis, and will revolutionize
long term follow-up? keratoprosthesis outcomes because of better biocompatibility,
JC: It happens that the majority of corneal blind live and lower physical profile in the eye. Future innovations will
in less financially well off communities. We have shown the include a change in physical design of the back plate with
cost utility of the Boston keratoprosthesis type I is excellent surface modifications to the titanium to improve both cosmesis
(~16,000 quality-adjusted life years), roughly equivalent to a and device retention.
corneal transplant, but still too expensive for less affluent parts QBM: Yes, as I mentioned earlier, we are making a new
of the world. I have been working on a $50 keratoprosthesis design called the CMP Kpro which incorporates some of the
design, we call the “Lucia”, which shows great promise, concepts of the Boston Kpro in the Pintucci model. However, I
but will not address the cost of postoperative medications have done only 2 so far, so it is too soon to share results.
and visits. The Boston keratoprosthesis type II has the same RT: We have initiated cost effective techniques for
cost utility as a hip replacement (~64,000 quality-adjusted ocular surface reconstructive procedures with cultured limbal
life years), and should be used selectively. Lastly, when epithelial cells and COMET for chemical burns. Biological
considering cost-effectiveness, one has also to consider the scaffold has been developed in collaboration with Stem Cell
cost benefit to patients and communities when the eyesight of Facility, AIIMS and IIT Delhi
blind individuals is restored. IS: Paralimbal Kpro is our innovation.
QBM: To give a bilaterally blind person sight, sometimes GI: We are in selected cases performing the Boston
after decades of darkness at a fraction of the cost of the same K-Pro through the oral mucosa.
procedure done abroad is an awesome feeling. This is the only I would like to acknowledge the entire Kpro team at
thing which keeps the handful of us doing these procedures in Sankara Nethralaya and specifically the ocular surface team –
India going. Financial rewards are nil as almost all bilaterally Drs. Bhaskar Srinivasan and Shweta Agarwal.
corneal blind patients in India belong to the economically
DOS Correspondent
Sana Ilyas Tinwala MD

www. dosonline.org l 15

Ocular OScuurlafraScuerfaDceiDsoisrodrdeer

Cell Based Therapy for Ocular Rajat Jain
Surface Reconstruction MS

1Rajat Jain MS, 2Shraddha Sureka MS, 2Anthony Vipin Das MS,
2Sayan Basu MS, 2Virender S. Sangwan MS

1. L.V. Prasad Eye Institute, Bhubaneshwar, India
2 L.V. Prasad Eye Institute, Hyderabad, India

Ocular surface reconstruction involves an entire gamut It acts as an interface between the eye and the outer world
of modalities, both medical and surgical. The principal and is unique that it is not protected by skin. The normal
goals of medical therapy would be supplementation of the functioning of the ocular surface requires an adequate tear
tear film, suppression of inflammation, limitation of tissue film, normal ocular adnexa, normal corneal sensitivity and
destruction and promotion of epithelial wound healing. The functioning limbal stem cells and hence a normal corneal
surgical approaches and techniques are varied and often epithelium (Figure 1).
performed as staged procedures. In this communication, we The limbus predominantly has two functions. It acts as a
discuss the principles in the approach to the management barrier between the avascular, smooth, non-keratinized and
of limbal stem cell deficiency disorders. goblet cell-free corneal epithelium and a mucin secreting,
Relevant anatomy of the ocular surface goblet cell rich conjunctival epithelium. It is also the source
The ocular surface functional unit consists of stratified of regenerating epithelial cells, from the stem cells, and
squamous corneal epithelium, limbal epithelium covering helps in maintaining of the corneal epithelium1-4.
the junction between corneal and conjunctival epithelium, Stem cells, present in all self-renewing tissues, are a
mucin producing conjunctival epithelium, muco- small subpopulation of specialized undifferentiated, self-
cutaneous junction of the lids which helps in the proper renewing cells with a slow cell cycle, long life span, a
spread of the tear film, lipid secreting meibomian glands, high capacity for error-free self renewal and a capability
aqueous secreting lacrimal glands and functioning eyelids. for asymmetric division1-4. They are capable of indefinite

Fig. 1 Fig. 2

Left Right
Figure 1: Figure showing the ocular surface which includes the tear film, eyelashes, eyelid margins, meibomian

glands and epithelial surfaces of conjunctiva and cornea
Figure 2: (Left) Anatomy of the limbus and the lineage of ‘Stem cells’; (Right) XYZ hypothesis

www. dosonline.org l 17

Ocular Surface Disorder

Table 1: Etiological Classification of Limbal Stem Cell was proposed by Thoft and Friend in 1983 as the ‘XYZ
Deficiency (LSCD) hypothesis’ (X+Y=Z)17. To ensure the normal health of
the tissue, cellular proliferation and differentiation in a
Primary LSCD Secondary LSCD coordinated manner at different levels of this hierarchy is
indispensable (Figure 2- Right).
Aniridia Trauma Limbal Stem Cell deficiency and classification
Inflammatory, infectious, traumatic or congenital
Multiple Endocrine Chemical – Acid and Alkali insult to these limbal cells may lead to limbal stem cell
Deficiency deficiency (LSCD). Limbal stem cell dysfunction should
be differentiated from limbal stem cell destruction. Limbal
Sclerocornea Thermal – Heat and Steam stem cell dysfunction is usually primary or hereditary
where the stem cells never achieve their normal function.
Erythrokeratoderma Radiation burns The condition is usually bilateral and less severe as the rest
of the ocular surface may be normal (e.g. aniridia, keratitis
Iatrogenic associated with multiple endocrinal deficiencies). Limbal
stem cell destruction is an acquired loss of functioning
Multiple ocular surgeries limbal stem cells. The condition can be unilateral or bilateral
and is associated with severe ocular surface damage (e.g.
Cyclocryotherapy chemical or thermal burns, Stevens Johnson Syndrome,
Ocular cicatricial pemphigoid, multiple surgeries, chronic
Use of topical Mitomycin C contact lens wear, etc.)1,18,19. LSCD could also be partial,
focal loss of limbal stem cells with rest of the limbus being
Systemic chemotherapy normal or total where there is total loss of limbal stem cells1.
The etiological classification of LSCD is given in Table 1.
Ocular Diseases Acute or chronic inflammatory damage to the stem cells
makes it less capable of healing and leads to severe scarring
Post infectious keratitis of the cornea, conjunctiva or the eyelids. In advanced
cases there may be destruction of the tear forming lacrimal
Neurotrophic keratitis glands leading to a dry ocular surface with progressive
dermalization or formation of a skin like rough surface as
Keratoconjunctivitis sicca seen in Stevens Johnson’s Syndrome and Ocular Cicatricial
Pemphigoid.
Severe (limbal) Vernal LSCD - clinical features
Keratoconjunctivitis The histological hallmark of LSCD is the presence of
conjunctival goblet cells on the corneal epithelium.
OSSN, Pterygium excision Impression cytology of the perilimbal area with nitrocellulose
acetate paper can detect the presence of goblet cells on
Chronic contact lens use the cornea20,21,22. However, the diagnosis of LSCD can
usually be established clinically and histological studies
Immune mediated are not required. Patients usually complain of redness,
(Systemic) irritation, foreign body sensation, photophobia decreased
vision and blepharospasm. The clinical hallmark of LSCD
Mucous Membrane is a triad of signs: conjunctivalisation, neovascularisation
Pemphigoid and chronic inflammation23-26. The fluorescein-stained
conjunctivalised cornea has a stippled appearance27-28 and
Stevens Johnson Syndrome there may be loss of palisades of Vogt in an area known
to have palisades prior to the insult29-30. In unilateral
Vitamin A Deficiency cases, it is useful to compare the limbus in the affected
quadrants with the corresponding areas of the unaffected
Idiopathic fellow eye. Other features include recurrent and persistent
epithelial defects, superficial vascularisation, scarring, thick
18Reproduced with permission fibrovascular pannus, ulceration, melting and perforation18.

proliferation to a large number of differentiated progeny,
responsible for cellular replacement and regeneration5-7.
Though there are no direct markers for the stem cells,
clinical8 and experimental evidence9-13 proves that the
corneal stem cell niche lies at the limbus, in the palisades
of Vogt14,15,16 (Figure 2 Left).
The asymmetric cell division of the limbal stem cells (SC)
allows one of the daughter cells to remain a stem cell
while the other cell differentiates to become a transient
amplifying cell (TAC) located in the corneal epithelial
basal layer. Both SCs and TACs are regarded as progenitor
cells and they give rise to post-mitotic cells (PMC) and
finally to terminally differentiated cells (TDC). The latter
two cell types are incapable of further cell division3. The
corneal epithelium is thus maintained by the balance of
proliferation of basal epithelial cells (X) and proliferation
and centripetal migration of limbal epithelial cells (Y)
with the loss of epithelial cells from the surface (Z). This

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Ocular Surface Disorder

Figure 3: Composite showing acute chemical injury with an Figure 4: Slit lamp image of limbal autografting with outcome
epithelial defect, corneal edema and surrounding limbal involvement (A): Schematic representation of the donor eye. The dotted lines represent
(A); partial limbal stem cell deficiency (LSCD) with central corneal the sites from which the donor conjunctival limbal autograft is harvested

scarring (B); total LSCD with fine pannus on the cornea (C); total (B): Schematic representation of the recipient eye- intra-operative
LSCD with thick pannus covering the whole corneal surface appearence. The donor tissue is anchored to the recipient bed in the

(D); total LSCD with granuloma, (E); total LSCD in a bone dry correct anatomical orientation with 10-0 monofilament nylon
ocular surface in a patient of Stevens Johnson Syndrome (F)
Previous studies have found that only 33 to 46% of corneal
Figure 3 represents a composite of figures representing grafts survive for one year and none survives after 3 years
varying degree of LSCD. after transplantation in eyes with ocular surface damage39.
This is in contrast to more common indications like corneal
Goals and Principles of management scars or keratoconus where the one year corneal graft
survival is more than 80%40. The management of limbal
The limbal stem cells are limited in number and do not stem cell deficiency depends on whether the condition is
regenerate. This makes the deficiency of limbal stem unilateral or bilateral, involving the visual axis and whether
cells impossible to treat by pharmacological means. The the ocular surface is wet or dry.
management of LSCD includes restoration of the damaged We describe below a review of the different cell based
ocular surface followed by subsequent definitive visual management strategies for ocular surface reconstruction.
rehabilitation, if required18. Unilateral Limbal Stem Cell deficiency
1. Limbal Autografting: The discovery of putative
Perhaps, the most important step in LSCD management is
to minimize the initial damage during the acute phase of epithelial stem cells in the palisades of Vogt
inflammation. Control of ocular surface inflammation with located in the limbus marked the beginning of the
the use of topical steroids and preservative free lubricating era of cell based therapy for the ocular surface
eye drops is advocated31. The various benefits of amniotic reconstruction11-16. Tsai RJ, et al conducted the first
membrane grafting in acute stage of chemical/thermal burn pre-clinical animal trial comparing the outcome of
or Stevens Johnson Syndrome has been established beyond limbal and conjunctival autograft transplantation
doubt32-38. In the authors experience, this simple surgical in corneal surface reconstruction and proved that
technique has a huge bearing on the long-term outcome of limbal transplantation had a better efficiency than
the ocular disease. conjunctival transplantation in restoring a destroyed
corneal surface41. Subsequently, Kenyon and Tseng for
Active inflammation could be detrimental to the the first time in 1989 transplanted two free limbal grafts
transplanted stem cells. Hence, any surgical treatment in that encompassed 8 clock hours of the recipient limbus
an inflamed eye will not give desired results. The success from the apparently healthy contralateral eye to and
of limbal transplantation further depends on concomitant proved that the corneal surface could be regenerated
lid pathology, dry eye and uncontrolled systemic disorders. by performing limbal transplantation42. Multiple
Hence, the management of LSCD also involves the reports of limbal autografting for ocular surface
treatment of associated adnexal conditions, management of disorders were then published43. Table 2 describes
dry eye and management of systemic diseases18. A detailed the clinical outcomes and complications of different
description of these conditions is outside the scope of this reports on limbal autografting. While autografting had
review. the obvious advantage of no risk of immunological
rejection and hence no need for long-term systemic
The deficiency of functional epithelial stem cells that occurs immunosuppression, many reports of iatrogenic donor
in these conditions is not met by corneal transplantation. site LSCD were however published44,47 (Figure 4).

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Ocular Surface Disorder

Table 2: Clinical outcomes and complications reported in studies on Limbal Auto-grafting

Author Year N Donor Clinical 2-line vision Complications (n) Follow-up (years)
tissue Success (%) gain (%) Mean (Range)
(Clock
hours)

Kenyon et al42 1989 26 4 77 65 None 18 (2 to 45)
Morgan et al43 1996 6 2 to 3 83
83 Donor site micro- NA (3 to 24)
9 2 to 4 77 perforation (1)

Tan et al42 1996 9 3 to 6 100 77 LSCD in donor 27.1 (2.5 to 46)
eye (1)
3 4 to 5 100
Frucht-Pery et 1998 100 None NA (15 to 60)
al45 1999
Basti et al46 100 Donor site NA (9 to 15)
conjuncti-
valization (1)

Rao et al47 1999 16 2 to 3 94 82 None 19.3 (3 to 45)
Dua et al48 2000 6 2 to 4 100
83 Filmentary 18.8 (14 to 31)
15 NA 87 keratitis (1)

Ozdemir et 2004 10 4 80 80 None 13.9 (3 to 24)
al49 12 4 100
Santos et al50 2005 25 2 to 4 NA 61 None 33 (NA)
Miri et al51 2010
Miri et al52 2011 81.3 None 3.9 (1 to 10)

NA Filamentary 41 (3 to 127)
keratitis (4), Donor
site conjuncti-
valization (17)

Welder et al53 2012 4 1.5 to 2 100 100 Nil 1.8 (0.6-2.6)

2. Ex-vivo Cultivation of autologous limbal epithelial or acquisition of prion diseases. Elimination of feeder
cells (Cultivated Limbal Epithelial Transplantation- cells and use of autologous human serum as an
CLET): The concerns regarding donor site complications alternative to FBS is therefore desirable. The authors
prompted the possibility of obtaining smaller biopsy have developed a cost-effective and safer xeno-free and
and expanding the cells ex-vivo on a suitable substrate feeder-free explant culture system that uses autologous
before transplanting them onto the affected eye. serum, recombinant enzymes and human growth
Since Pellegrini and co-workers54 first described their factors and is devoid of animal-derived products. It is
technique, several groups around the world have a submerged culture technique which also promotes
described various techniques of culturing limbal stem stem cell maintenance. The surgery, in brief, consists
cells. The technique of cultivation could either be a of the following steps: a 2x2 mm biopsy is taken from
suspension culture or an explant culture. Xenogenic the superior limbus. The conjunctiva is incised and a
constituents of a limbal culture system may be in the sub-conjunctival dissection is continued until limbus is
form of murine feeder cells55-57, fetal bovine serum reached. Subsequently, a shallow dissection is carried
(FBS)55-59 or animal-derived growth factors60. Table 3 out 1 mm into the clear cornea. The tissue is transported
describes the clinical outcomes of reported studies on to the laboratory in human corneal epithelium (HCE)
autologous cultivated limbal epithelial transplantation medium. Under strict aseptic conditions, the donor
using such animal-derived growth factors. limbal tissue is shredded into small pieces. Indigenously
prepared human amniotic membrane (hAM), is used as
Animal derived products in a cell culture system a carrier. It sheet is de-epithelised and the shredded
always have a theoretical risk of infection, rejection

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Ocular Surface Disorder

Table 3: Clinical outcomes of reported studies on autologous cultivated limbal epithelial transplantation using Animal-derived
growth factors

Author Year Culture Substrate Eyes Clinical 2-line visual Follow-up (months)
Technique Success gain (%) Mean (Range)

(%)

Pellegrini et al54 1997 Suspension 3T3s 2 100 50 24 NA

Schawb et al60 1999 Suspension hAM 17 76 16 10 2-24

Schawb et al61 2000 Suspension hAM 10 60 36 13 6-19

Tsai et al62 2000 Explant hAM 6 100 50 15 12-18

Rama et al63 2001 Suspension Fibrin 18 74 33 17.5 12-27

Grueterich et al64 2002 Explant hAM 1 100 100 21 NA

Sangwan et al65 2003 Explant hAM 2 100 50 29.5 25-34

Nakamura et al66 2004 Explant hAM 1 100 100 19 NA

Sangwan et al58 2006 Explant hAM 88 73 37 29.5 25-34

Kawashima et al67 2007 Explant hAM 2 100 67 23 5-41

Shortt et al68 2008 Suspension hAM 3 67 33 6 1-10

Gisoldi et a69 2010 Suspension Fibrin 6 83 83 24 11-34

Rama et al70 2010 Suspension Fibrin 107 68 54 35 12 to 120

Di Iorio et al71 2010 Suspension Fibrin 166 80 NA 29.9 6-50

Pauklin et al72 2010 Explant hAM 30 77 73 28.5 10-72

Barandan-Rafii et 2010 Explant hAM 8 88 63 34 6-48
al73

Meller et al74 2010 ***(full text not hAM 30 76.7 NA 28.9 NA
available)

Thanos M, et al75 2010 1 100 100 28 NA

Prabhaswat et al76 2012 Explant hAM 12 58.3 NA 25.8 6-46

Marchini et al77 2012 NA Fibrin 16 71.3 50 NA 12-50

Sharma S et al78 2013 ***(full text not available) 4 100 # needed 19.5 9-26
DALK

Table 4: Clinical outcomes of reported studies on autologous cultivated limbal epithelial transplantation using completely xeno-free
cultiation techniques

Author Year Culture Substrate Eyes Clinical 2-line visual Follow-up (months)

Technique Success (%) gain (%) Mean Range

Nakamura et al79 2006 Explant hAM 2 100 67 15 14-16

Shimakazi et al80 2007 Explant hAM 16 50 37.5 30 6-86

Di Girolamo et al81 2009 Explant CL 2 100 50 10 8 - 13

Kolli et al82 2010 Explant hAM 8 100 63 19 12-30

Sangwan et al83 2011 Explant hAM 200 71 60.5 34 12-91

Subramanium SV et al85 2013 Explant hAM 40 NA* NA* 33 1-87

Sejpal K et al86 2013 Explant hAM 107 46.7 54.2 41.2 12-118

bits of limbal tissue are explanted over the centre of CmOon2 oalnayder95o%f air. The culture is completed when a
de-epithelised hAM with the basement membrane the cells growing from the explants
side up. A similar parallel culture is also prepared as became confluent, typically in 10 to 14 days83,84. In
a backup. The culture is incubated at 370C with 5% the recipient eye, a 3600 peritomy is performed and

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Ocular Surface Disorder

Figure 5: CLET - Clinical photographs of eyes before and after autologous cultivated limbal epithelial transplantation.
Eyes of four different patients with total limbal stem cell deficiency and variable amounts of corneal stromal scarring
(A to D); same eyes 1 year after limbal transplantation (E to H); Right eye of a 26-year-old female patient with a history
of alkali injury showing a stable corneal surface, minimal stromal scarring and a best-corrected visual acuity (BCVA)
of 20/30 (E). Right eye of a 19-year-old male patient with a history of acid injury showing a stable corneal surface with
residual stromal scarring with a BCVA of 20/100 (F). Right eye of a 45-year-old male patient with a history of alkali
injury showing recurrence of conjunctivalisation inferiorly (failure) between 4 and 7 o’clock at the limbus, with a BCVA
of 20/40 (G). Right eye of a 37-year-old female patient with a history of acid injury showing a stable corneal surface and a
clear corneal graft with a BCVA of 20/20 (H). Reproduced with permission from Br J Ophthalmol. 2011;5:1525-9.

the vascular pannus covering the cornea is removed. technique of limbal transplantation, In-vivo Cultivation
Bleeders are cauterized. Human amniotic membrane of autologous limbal epithelial cells (Simple Limbal
(hAM) graft is then placed over the bared ocular surface epithelial Transplantation -SLET), which combines the
and is secured with fibrin glue (TISSEEL Kit from Baxter advantages of conjunctival limbal autografting (CLAU)
AG, Vienna, Austria). The donor tissue is then cut into and cultivated limbal epithelial transplantation (CLET)
eight to ten small pieces and these limbal transplants by being a single-stage, easily affordable procedure
are placed, epithelial side up, on the hAM, sparing the which utilizes a minimal donor tissue and does not
visual axis. These transplants are also fixed in place need a stem cell laboratory for cultivation of limbal
with fibrin glue. A soft bandage contact lens is placed epithelial cells.
on the recipient eye. The surgical steps were similar to those of CLET. A
Table 4 describes the outcomes of reported studies on 2x2 mm limbal biopsy is harvested, in the similar
autologous cultivated limbal epithelial transplantation fashion as described earlier, and is placed in balanced
using a completely xeno-free explant culture technique. salt solution. In the recipient eye, human amniotic
Although, comparing success rates among different membrane (hAM) graft is then placed over the bared
culture techniques may be misleading as the indications ocular surface and is secured with fibrin glue (TISSEEL
for surgery, sample size, and follow-up duration are Kit from Baxter AG, Vienna, Austria). The donor tissue
variable among different studies; it does appear there is subsequently cut into eight to ten small pieces and
is no clinical advantage that one technique has over these limbal transplants are placed, epithelial side up,
the other (Figure 5). on the hAM, sparing the visual axis. These transplants
3. In-vivo Cultivation of autologous limbal epithelial are also fixed in place with fibrin glue. A soft bandage
cells: Sangwan et al87 proposed a novel simplified contact lens is placed on the recipient eye (Figure 6).

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Ocular Surface Disorder

Figure 6: Composite of intra-operative photographs describing the surgical steps of Simple Limbal Epithelial Transplantation (SLET).
(A): 2x2 mm area is marked in superior limbus of the donor eye; (B): sub-conjunctival dissection is carried out 1 mm into the clear
cornea; (C): The limbal tissue is excised; (D, E): peritomy is performed and fibrovascular pannus is excised from the recipient ocular
surface; (F): human amniotic membrane graft is placed on the bare ocular surface and secured with fibrin glue;

(G, H): donor limbal tissue is cut into eight to ten small pieces and secured to amniotic membrane overlying the cornea with fibrin glue.
(Reproduced with permission from Br J Ophthalmol.2012;96(7):931-4)

Figure 7: Composite showing a patient of chemical injury induced In the only study published on SLET thus far,87 the
LSCD who underwent SLET. (A): Pre-operative image showing authors treated 6 patients of unilateral and total limbal
limbal stem cell deficiency with symblepharon formation; (B): In-vivo stem cell deficiency following ocular surface burns. A
cultivation of limbal stem cells (SLET) - post-operative day 1 picture completely epithelialised, avascular and stable corneal
surface was seen in all recipient eyes by 6 weeks and
showing explants in place on an intact amniotic membrane; was maintained at a follow-up of 9.2 + 1.9 months.
(C): post-operative day 14 picture showing explants in place, cornea Subsequently isolated case reports have been published
getting clear and an amniotic membrane which is degenerating, best for this technique88-90. Although long-term results
corrected visual acuity – 20/200; (D): post-operative 2 months image are awaited, simple limbal epithelial transplantation
showing a relatively clear corneal with remnants of explants in place, promises to be an easy and effective technique for
treating unilateral limbal stem cell deficiency following
best corrected visual acuity – 20/30 ocular burns (Figure 7).

Bilateral Limbal Stem Cell Deficiency
1. Allogenic transplantation: In eyes with bilateral LSCD,

there is no autologous source of limbal cells which
can be used for therapy. These patients can either be
treated with allogenic limbal transplantation, from
living (related or unrelated) or cadaveric donors, or
with autologous transplantation of epithelial cells of
a different lineage, like oral or nasal mucosa. Living
donors are preferable as limbal cells obtained from
cadavers have a lower proliferative rate in vitro91 and
a poorer corneal epithelisation rate in vivo92,93. Table 5
describes the clinical outcomes reported in studies on
allogenic cultivated limbal epithelial transplantation
(Figure 8).
The advantage of autologous transplantation of oral or
nasal mucosa is that there is no risk of immunological

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Ocular Surface Disorder

Figure 8: Postoperative clinical photographs of four eyes that underwent allogeneic cultivated limbal
epithelial transplantation, followed by penetrating keratoplasty (PK) for limbal stem cell deficiency

(LSCD). (Reproduced with permission from Br J Ophthalmol 2012;96:1504–1509)

Table 5: Clinical outcomes reported in studies on Allogenic Cultivated Limbal Epithelial Transplantation

Author Year Donor Method Xeno-Free N Success (%) Follow-Up
(months)

Tsai et al94 1994 Cadaveric NA NA 16 62.5 18.5 (NA)
Tan et al95 1996 Cadaveric NA NA 9 77.7 14.7
Schwabb, et al60 1999 LR Suspension No 2 50 13 (16-19)
Schwabb, et al61 2000 LR Suspension No 4 100 10.5 (2-24)
Koizumi, et al96 2001 Cadaveric Explant No 13 92 11.2 (9-13)
Koizumi, et al97 2001 Cadaveric Explant No 3 100 6
Shimazaki et al98 2002 Cadaveric 13
Nakamura, et al99 2003 Cadaveric Explant No 3 100 13 (12-14)
Sangwan, et al100 2005 LR 4 100 15.3 (7-24)
Daya, et al101 2005 1 LR, 9 Cadaveric Explant Yes 10 70 28 (12-50)
Nakamura, et al79 2006 Cadaveric 7 100 14.6 (6-26)
Shimazaki, et al102 2007 7 LR, 7 Cadaveric Suspension No 20 50 29 (6-85)
Ang, et al103 2007 Cadaveric 1 100 48
Kawashima et al67 2007 LR 1, Cadaveric 3 Suspension No 4 100 26 (15-33)
Shortt, et al68 2008 Cadaveric 7 71 10 (6-13)
Meller, et al104 2009 HLA-Donor Explant Yes 1 100 31
Pauklin, et al72 2010 4 LR, 10 Cadaveric 14 50 28.5 (9-72)
Miri A et al105 2010 9 LR, 6 Cadaveric Suspension No 15 NA 30.8 (13-96)

LR Explant Yes 28 71.4 58 (2-114)

Explant No

Explant Yes

Explant No

Non cultivated, Allolimbal
transplantation

Basu S et al106 2011 Explant Yes

rejection and hence no need for systemic lineages107-110 until Nakamura et al111,112 developed
immunosuppression, unlike allogenic transplantation. the cultivated oral mucosal epithelial transplantation
However, these transplanted cells often maintain (COMET) procedure. It is a safe and effective means of
their original phenotype, invite vascularization and managing patients with severe bilateral LSCD following
therefore provide poor visual outcomes. chemical injuries with good clinical outcome in terms
2. Cultivated Oral Mucosal Epithelial Transplantation of ocular surface stabilization, symptomatic relief and
(COMET): There had been earlier attempts of a marginal improvement in visual acuity. Table 6
autografting in bilateral LSCD with different non-corneal enumerates the different studies published for COMET
in bilateral LSCD.

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Figure 9: Preoperative (a,b): clinical photograph of right and left eye old female who presented one year following bilateral
showing bilateral limbal stem cell deiciency. (c): Post-operative view of chemical injury with alkali. One month later her
right eye showing an epithelialised central cornea with residual deep unaided visual acuity (VA) improved to 20/100 from
stromal scarring and few limbal transplants persisting over the cornea. hand-motions preoperatively with a stable, avascular
(d): Circumcorneal congestion with engorged, tortuous perilimbal vessels and epithelialized corneal surface. Three months later,
(arrow) and 3600 peripheral superficial corneal neovascularisation. (e): Fine she presented with allograft rejection suggested by
vascular ingrowths from the perilimbal area approaching the peripheral acute pain with peripheral corneal neovascularization
limbal transplants (arrow). (f): Well epithelialised ocular surface with decrease encircling the transplants, engorged and tortuous peri-
in congestion and persistence of neovascularisation following systemic limbal vessels and diffuse epithelial haze. Rejection
immunosuppression. (Reproduced with permission from BMJ Case Rep. episode was reversed with pulse doses of intravenous
methyl prednisolone with intensive topical steroids in
2013 Mar 14;2013. a week. She recovered to her pre-rejection VA. She
was later maintained on systemic immunosuppressive
Authors have earlier also performed allogenic agents. This case describes the clinical features of
(cadaveric) SLET for bilateral limbal stem cell allograft rejection following SLET and emphasizes
deficiency90. It was done in the right eye for a 41 year the importance of continued immunosuppression in
allogeneic limbal transplantation (Figure 9).
3. Boston Keratoprosthesis: is one of the non-cell based
options in the management of bilateral LSCD. Boston
type I keratoprosthesis gives superior visual outcomes
in the management of corneal LSCD when compared
with other treatment modalities126. In spite of the
different complications associated with this technique,
like retroprosthetic membrane formation (26.7%),
sterile corneal stromal necrosis (17.8%), and elevated
intraocular pressure (13.9%),127 the authors believe that
it is still a safe and an effective long-term management

Table 6: Cultivated Oral Mucosal Epithelial transplantation – COMET – for bilateral LSCD

Author Year Culture Eyes Clinical 2-line visual Follow-up (months)

technique Success (%) gain (%) Mean Range

Nakamura et al113 2004 6 100 100 13.8 11-17

Nishida et al114 2004 3t3 + MMC 4 100 100 14 13-15

Inatomi et al115 2006 3t3 + MMC 15 67 67 20 3-34

Inatomi et al116 2006 3t3 + MMC 2 100 0 (improved after 22.5 NA
second surgery)

Ma et al117 2009 5 80 NA 29.6 26-34
12 NA
Uchino et al117 2009 1 100 100 14.2 10-22
55 36-90
Chen HCJ et al11 2009 4 100 NA 25.5 6-54.9
30 NA
Nakamura et al120 2011 3t3 + MMC 19 100 42 64 NA

Satake et al121 2011 3t3 + MMC 40 57.5 59

Takeda K et al122 2011 3t3 + MMC 3 67 0

Hirayama et al123 2012 3t3 + MMC 16 62.5 68.8
(Substrate free)

Hirayama et al123 2012 3t3 + MMC 16 37.5 43.8 85.5 NA
(hAM)

Burillon C et al124 2012 25 64 38.46 12 NA
28.7 (6.2 – 85.6)
Sotozono et al125 2013 46 NA NA (Improvement in
48%)

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Ocular Surface Disorder

Figure 10: Composite showing a slit lamp image of left eye of a patient who had a bilateral LSCD due to chemical injury (A); image after the
patient had undergone multiple penetrating keratoplasties and limbal transplantation (cadaveric and living related) procedures (B); post-
operative day 1 picture after Boston Keratoprosthesis, BCVA 20/40 (C); post-operative 41 months picture after Boston Keratoprosthesis,
BCVA 20/20. (D); (Reproduced with permission from BMJ Case reports 2013 May 29;2013).

Figure 11 (A): Slit lamp image of a patient of SJS a plate as a carrier for a PMMA optical cylinder. The
(B): who underwent MOOKP implantation surgery involves different stages done over a period
of 8-10 months. Details of the surgery are beyond the
option for patients of bilateral non–immune-mediated scope of this review. In a series of 234 patients, with a
limbal stem cell deficiency128 (Figure 10). median follow-up from stage II of 9.4 + 5.7 years, an
4. Osteo-Odonto Keratoprosthesis (OOKP): For patients anatomic success of more than 94% was reported135.
with bilateral LSCD with a severe dry ocular surface, Visual acuity was more than 6/18 in 52% (range 46-
Strampelli129-133 and Falcinelli134 developed the OOKP. 72%) of the eyes with OOKP surgery. However,
The principle of OOKP is the use of a single rooted the most common intraoperative complication was
tooth and surrounding intact alveolar bone to fashion vitreous hemorrhage (0-52%) and the most common
long-term blinding complication was glaucoma (7-
47%). Endophthalmitis rates ranged from 2-8%
(Figure 11).
Conclusion
Ocular surface reconstruction for the purpose of cosmetic
and visual rehabilitation is a challenging prospect for both,
the surgeon as well as the patient. Current knowledge of
the ocular surface components and pathophysiological

Figure 12: Authors’ treatment algorithm for the management Figure 13: Authors’ treatment algorithm for the management of
of unilateral or bilateral LSCD in a wet ocular surface unilateral or bilateral LSCD in an ocular surface with severe dry eye

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Ocular Surface Disorder

mechanisms has led to tremendous advancements in the 23. Chen JJ, Tseng SC. Corneal wound healing in partial limbal
management of ocular surface disorders (OSD). deficiency. Invest Ophthalmol Vis Sci. 1990;31:1301-14.

The treatment algorithms given in (Figure 12&13) 24. Chen JJ, Tseng SC. Abnormal corneal epithelial wound healing in
elucidate the authors’ treatment protocols in these cases. partial-thickness removal of limbal epithelium. Invest Ophthalmol
Of the different management options discussed in this Vis Sci. 1991;32:2219-33.
communication, In-vivo Cultivation of autologous limbal
epithelial cells (SLET) and Boston Keratoprosthesis remain 25. Huang AJ, Tseng SC. Corneal epithelial wound healing in the absence
the authors’ preference for the management of unilateral or of limbal epithelium. Invest Ophthalmol Vis Sci. 1991;32:96-105.
bilateral LSCD respectively.
26. Kruse FE, Chen JJ, Tsai RJ, Tseng SC. Conjunctival transdifferentiation
References is due to the incomplete removal of limbal basal epithelium. Invest
Ophthalmol Vis Sci. 1990;31:1903-13.
1. Dua HS, Azuara-Blanco A. limbal stem cells of corneal epithelium.
Surv Ophthalmol. 2000;44:415-25. 27. Dua HS, Gomes JA, Singh A. Corneal epithelial wound healing. Br J
Ophthalmol. 1994;78:401-8.
2. Kinoshita S, Friend J, Thoft RA. Biphasic cell proliferation in
transdifferentiation of conjunctival to corneal epithelium in rabbits. 28. Dua HS, Forrester HV. The corneo-scleral limbus in human corneal
Invest Ophthalmol Vis Sci. 1983;24:1008-14. epithelial wound healing. Am J Ophthalmol. 1990;110:646-56.

3. Leblond CP. The life history of cells in renewing systems. Am J Anat. 29. Tseng SCG, Chen JJY, Huang AJW, et al. Classification of conjunctival
1981:160:114-158. surgeries for corneal disease based on stem cell concept. Ophthalmol
Clin North Am. 1990;3:595-610.
4. Potten CS. Epithelial proliferative subpopulations. In Stem Cells And
Tissue Hemostasis, Cambridge 1978, Cambridge university press, 30. Kinoshita S, Kiritoshi A, Ohji M, et al. Disappearance of palisades of
page 317. Vogt in ocular surface disease. Jpn J Clin Ophthalmol. 1986;40:363-
66.
5. Potten CS, Leoffler M. Epithelial Cell Prolifration. Changes with time
in the proportaion of isolated, paired and clustered labelled cells in 31. Sangwan VS, Matalia, HP, Vemuganti GK, et al. Early results
sheets of murine epidermis. Virchows Arch [B]. 1987;53:286:300. of penetrating keratoplasty after cultivated limbal epithelial
transplantation. Arch Ophthalmol. 2005;123(3):334-40.
6. Potten CS, Morris RJ. Epithelial stem cells in vivo. J Cell
Sci.1988;10(supp):45-62. 32. Tamhane A, Vajpayee RB, Biswas NR, et al. Evaluation of amniotic
membrane transplantation as an adjunct to medical therapy as
7. Pfister RR. Corneal stem cell disease: concepts, categorization and compared with medical therapy alone in acute ocular burns.
treatment by auto- and homo- transplantation of limbal stem cells. Ophthalmology 2005;112:1963-9.
CLAO J. 1994;20:64-72.
33. Meller D, Pires RT, Mack RJ, et al. Amniotic membrane
8. Davanger M, Evensen A. Role of pericorneal papillary structure in transplantation for acute chemical or thermal burns.Ophthalmology
renewal of corneal epithelium. Nature 1971;229:560-1. 2000;107:980-9.

9. Lee GA, Hirst LW. Ocular surface squamous neoplasia. Surv 34. John T, Foulks GN, John Me, et al. Amniotic membrane in the surgical
Ophthalmol. 1995;39:429-50. management of acute toxic epidermal necrolysis. Ophthalmology
2002;109:351-60.
10. Schermer A, Galvin S, Sun TT. Differentiation-related expression of
a major 64K corneal keratin in vivo and in culture suggests limbal 35. Kobayashi A, Yoshita T, Sugiyama K, et al. Amniotic membrane
location of corneal epithelial cells. J Cell Biol. 1986;103:49-62. transplantation in acute phase of toxic epidermal necrolysis with
severe corneal involvement. Ophthalmology 2006;113:126-32.
11. Kurpakus MA, Stock EL, Jones JC. Expression of the 55-kD/64-kD
corneal keratins in ocular surface epithelium. Invest Ophthalmol Vis 36. Muquit M, Ellingham R, Daniel C. Technique of amniotic membrane
Sci. 1990;31:448-56. transplant dressing in the management of acute Stevens-Johnson
syndrome. Br J Ophthalmol. 2007;91:1536.
12. Ebato B, Friend J, Thoft RA. Comparison of central and peripheral
human corneal epithelium in tissue culture. Invest Ophthalmol Vis 37. Tandon A, Cackett P , Mulvihill A, Fleck B. amniotic membrane
Sci. 1987;28:1450-6. grafting for conjunctival and lid surface disease in the acute phase of
toxic epidermal necrolysis. J AAPOS 2007;11:612-3.
13. Ebato B, Friend J, Thoft RA. Comparison of limbal and peripheral
human corneal epithelium in tissue culture. Invest Ophthalmol Vis 38. Shay E, Khadem JJ, Tseng SC. Efficacy and limitation of sutureless
Sci. 1988;29:1533-7. amniotic membrane transplantation for acute toxic epidermal
necrolysis. Cornea 2010;29:359–61.
14. Cotsarelis G, Cheng SZ, Dong G, Sun TT, Lavker RM. Existence of
slow-cycling limbal epithelial basal cells that can be preferentially 39. Brown SI, Bloomfield SE, Pearce DB. Follow-up report
stimulated to proliferate: Implications of epithelial stem cells. Cell on transplantation of the alkali burned cornea. Am J
1989;57:201-9. Ophthalmol.1974;77:538-42.

15. Schofield R. The stem cell system. Biomed Pharamcother. 40. Mahmood MA, Wagoner MD. Penetrating keratoplasty in
1983;37:375-80. eyes with keratoconus and vernal keratoconjunctivitis. Cornea
2000;19:468–70.
16. Schlotzer-Schrehardt U, Kruse FE. Identification and characterisation
of limbal stem cells. Exp Eye Res. 2005;81:247-64. 41. Tsai RJ, Sun TT, Tseng SC. Comparison of limbal and conjunctival
autograft transplantation in corneal surface reconstruction in rabbits.
17. Thoft RA, Friend J. The X,Y,Z hypothesis of corneal epithelial Ophthalmology 1990;97(4):446-55.
maintenance. Invest Ophthal Vis Sci. 1983;24:1442-3.
42. Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular
18. Fernandes M, Sangwan VS, Rao SK, et al. Limbal Stem Cell surface disorders. Ophthalmology 1989;96(5):709-22.
Transplantation. Indian J Ophthalmol. 2004;52:5-22.
43. Morgan S, Murray A. Limbal autotransplantation in the acute and
19. Kruse EF. Stem cells and corneal regeneration. Eye 1994;8:170-83. chronic phases of severe chemical injuries. Eye (Lond).1996;10 ( Pt
20. Puangsricharern V, Tseng SC. Cytologic evidence of corneal disease 3):349-54.

with limbal stem cell deficiency. Ophthalmology 1995;102:1476- 44. Tan DT, Ficker LA, Buckley RJ. Limbal transplantation.
85. Ophthalmology 1996;103(1):29-36.
21. Egbert PR, Lauber S, Maurice DM. A simple conjunctival biopsy. Am
J Ophthalmol. 1977;84:798-80. 45. Frucht-Pery J, Siganos CS, Solomon A, et al. Limbal cell autograft
22. Tsubota K, Toda I, Saito H, Shinozaki N, Shimazaki J. Reconstruction transplantation for severe ocular surface disorders. Graefes Arch Clin
of the corneal epithelium by limbal allograft transplantation for Exp Ophthalmol. 1998;236(8):582-7.
severe ocular surface disorders. Ophthalmology 1995;102:1486-96.
46. Basti S, Mathur U. Unusual intermediate-term outcome in
three cases of limbal autograft transplantation. Ophthalmology.
1999;106(5):958-63.

47. Rao SK, Rajagopal R, Sitalakshmi G, Padmanabhan P. Limbal
autografting: comparison of results in the acute and chronic phases
of ocular surface burns. Cornea 1999;18(2):164-71.

www. dosonline.org l 27

Ocular Surface Disorder

48. Dua HS, Azuara-Blanco A. Autologous limbal transplantation in 71. Di Iorio E, Ferrari S, Fasolo A, et al. Techniques for culture and
patients with unilateral corneal stem cell deficiency. Br J Ophthalmol. assessment of limbal stem cell grafts. Ocul Surf. 2010;8(3):146-53.
2000;84(3):273-8.
72. Pauklin M, Fuchsluger TA, Westekemper H, et al. Midterm
49. Ozdemir O, Tekeli O, Ornek K, et al. Limbal autograft and results of cultivated autologous and allogeneic limbal epithelial
allograft transplantations in patients with corneal burns. Eye (Lond). transplantation in limbal stem cell deficiency. Dev Ophthalmol.
2004;18(3):241-8. 2010;45:57-70.

50. Santos MS, Gomes JA, Hofling-Lima AL, et al. Survival analysis of 73. Baradaran-Rafii A, Ebrahimi M, Kanavi MR, et al. Midterm outcomes
conjunctival limbal grafts and amniotic membrane transplantation of autologous cultivated limbal stem cell transplantation with or
in eyes with total limbalstem cell deficiency. Am J Ophthalmol. without penetrating keratoplasty. Cornea 2010;29:502–9.
2005;140(2):223-30.
74. Meller D, Pauklin M, Westekemper H, et al. Autologous
51. Miri A, Al-Deiri B, Dua HS. Long-term outcomes of autolimbal and Transplantation of cultivated limbal epithelium. Ophthalmologe.
allolimbal transplants. Ophthalmology 2010;117(6):1207-13. 2010;107(12):1133-8 [Article in German].

52. Miri A, Said DG, Dua HS. Donor site complications in autolimbal 75. Thanos M, Pauklin M, Steuhl KP, et al. Ocular Surface Reconstruction
and living-related allolimbal transplantation. Ophthalmology With Cultivated Limbal Epithelium in a Patient With Unilateral
2011;118(7):1265-71. Stem Cell Deficiency Caused by Epidermolysis Bullosa Dystrophica
Hallopeau-Siemens. Cornea 2010;29:462–464.
53. Welder JD, Pandya HK, Nassiri N, Djalilian AR. Conjunctival limbal
autograft and allograft transplantation using fibrin glue. Ophthalmic 76. Prabhasawat P, Ekpo P, Uiprasertkul M, et al. Efficacy of cultivated
Surg Lasers Imaging 2012;43(4):323-7. corneal epithelial stem cells for ocular surface reconstruction. Clin
Ophthalmol. 2012;6:1483-92.
54. Pellegrini G, Traverso CE, Franzi AT, et al. Long-term restoration
of damaged corneal surfaces with autologous cultivated corneal 77. Marchini G, Pedrotti E, Pedrotti M, et al. Long-term effectiveness
epithelium. Lancet 1997;349:990-3. of autologous cultured limbal stem cell grafts in patients with
limbal stem cell deficiency due to chemical burns. Clinical and
55. Rama P, Matuska S, Paganoni G, et al. Limbal stem-cell therapy and Experimental Ophthalmology 2012; 40: 255–67.
long-term corneal regeneration. N Engl J Med. 2010;363:147-55.
78. Sharma S, Tandon R, Mohanty S, et al. Phenotypic evaluation
56. Di Iorio E, Ferrari S, Fasolo A, et al. Techniques for culture and of severely damaged ocular surface after reconstruction by
assessment of limbal stem cell grafts. Ocul Surf. 2010;8:146-53. cultured limbal epithelial cell transplantation. Ophthalmic Res.
2013;50(1):59-64.
57. Baradaran-Rafii A, Ebrahimi M, Kanavi MR, et al. Midterm outcomes
of autologous cultivated limbal stem cell transplantation with or 79. Nakamura T, Inatomi T, Sotozono C, et al. Transplantation of
without penetrating keratoplasty. Cornea 2010;29:502-9. autologous serum-derived cultivated corneal epithelial equivalents
for the treatment of severe ocular surface disease. Ophthalmology
58. Sangwan VS, Matalia HP, Vemuganti GK, et al. Clinical outcome 2006;113:1765-72.
of autologous cultivated limbal epithelium transplantation. Indian J
Ophthalmology 2006;54:29-34. 80. Shimazaki J, Higa K, Morito F, et al. Factors influencing outcomes
in cultivated limbal epithelial transplantation for chronic cicatricial
59. Pauklin M, Fuchsluger TA, Westekemper H, et al. Midterm ocular surface disorders. Am J Ophthalmol. 2007;143:945-53.
results of cultivated autologous and allogeneic limbal epithelial
transplantation in limbal stem cell deficiency. Dev Ophthalmology 81. Di Girolamo N, Bosch M, Zamora K, et al. A contact lens-based
2010;45:57-70. technique for expansion and transplantation of autologous epithelial
progenitors for ocular surface reconstruction. Transplantation
60. Schwab IR. Cultured corneal epithelia for ocular surface disease. 2009;87:1571-8.
Trans Am Ophthalmol Soc. 1999; 97:891-986.
82. Kolli S, Ahmad S, Lako M, et al. Successful clinical implementation
61. Schwab IR, Reyes M, Isseroff RR. Successful transplantation of of corneal epithelial stem cell therapy for treatment of unilateral
bioengineered tissue replacements in patients with ocular surface limbal stem cell deficiency. Stem Cells 2010;28:597-610.
disease. Cornea 2000;19:421-6.
83. Sangwan VS, Basu S, Vemuganti GK, et al. Clinical outcomes of
62. Tsai RJ, Li LM, Chen JK: Reconstruction of damaged corneas by xeno-free autologous cultivated limbal epithelial transplantation: a
transplantation of autologous limbal epithelial cells. N Engl J Med. 10-year study. Br J Ophthalmol. 2011;95(11):1525-9.
343:86--93, 2000.
84. Mariappan I, Maddileti S, Savy S, et al. In vitro culture and expansion
63. Rama P, Bonini S, Lambiase A, et al: Autologous fibrin-cultured limbal of human limbal epithelial cells. Nature Protocols 2010;5(8): 1470-
stem cells permanently restore the corneal surface of patients with 9.
total limbal stem cell deficiency. Transplantation 2001;72:1478-85.
85. Subramaniam SV, Sejpal K, Fatima A, et al. Coculture of autologous
64. Grueterich M, Espana EM, Touhami A, et al. Phenotypic study of limbal and conjunctival epithelial cells to treat severe ocular surface
a case with successful transplantation of ex vivo expanded human disorders: long-term survival analysis. Indian J Ophthalmol. 2013
limbal epithelium for unilateral total limbal stem cell deficiency. May;61(5):202-7.
Ophthalmology 2002;109:1547-52.
86. Sejpal K, Ali MH, Maddileti S, Basu S, et al. Cultivated limbal
65. Sangwan VS, Vemuganti GK, Iftekhar G, et al. Use of autologous epithelial transplantation in children with ocular surface burns.
cultured limbal and conjunctival epithelium in a patient with severe JAMA Ophthalmol. 2013;131(6):731-6.
bilateral ocular surface disease induced by acid injury: a case report
of unique application. Cornea 22:478--81, 2003. 87. Sangwan VS, Basu S, MacNeil S, et al. Simple limbal epithelial
transplantation (SLET):a novel surgical technique for the treatment
66. Nakamura T, Inatomi T, Sotozono C, et al. Successful primary culture of unilateral limbal stem cell deficiency. BJO.2012;96(7):931-4.
and autologous transplantation of corneal limbal epithelial cells
from minimal biopsy for unilateral severe ocular surface disease. 88. Lal I, Panchal BU, Basu S, Sangwan VS. In-vivo expansion
Acta Ophthalmol Scand. 2004;82:468-71. of autologous limbal stem cell using simple limbal epithelial
transplantation for treatment of limbal stem cell deficiency. BMJ
67. Kawashima M, Kawakita T, Satake Y, Higa K, Shimazaki J. Phenotypic Case Rep. 2013 May 22;2013.
study after cultivated limbal epithelial transplantation for limbal
stem cell deficiency. Arch Ophthalmol. 2007;125:1337–44. 89. Bhalekar S, Basu S, Lal I, Sangwan VS. Successful autologous
simple limbal epithelial transplantation (SLET) in previously failed
68. Shortt AJ, Secker GA, Rajan MS, et al. Ex vivo expansion and paediatric limbal transplantation for ocular surface burns. BMJ Case
transplantation of limbal epithelial stem cells. Ophthalmology Rep. 2013 May 10;2013.
2008;115(11):1989-97.
90. Bhalekar S, Basu S, Sangwan VS. Successful management of
69. Gisoldi RAM C, Pocobelli A, Villani CM, Amato D, Pellegrini G. immunological rejection following allogenic simple limbal epithelial
Evaluation of molecular markers in corneal regeneration by means transplantation (SLET) for bilateral ocular burns. BMJ Case Rep. 2013
of autologous cultures of limbal cells and keratoplasty. Cornea Mar 14;2013.
2010;29:715–22.

70. Rama P, Matuska S, Paganoni G, et al. Limbal stem-cell therapy and
long-term corneal regeneration. N Engl J Med. 2010;363(2):147-155

28 l DOS Times - Vol. 19, No. 4 October, 2013

Ocular Surface Disorder

91. Vemuganti GK, Kashyap S, Sangwan VS, et al. Ex-vivo potential of 114. Nishida K, Yamato M, Hayashida Y, et al. Corneal Reconstruction
cadaveric and fresh limbal tissues to regenerate cultured epithelium. with Tissue Engineered Cell Sheets Composed of Autologous Oral
Ind J Ophthalmol. 2004;52:113–20. Mucosal Epithelium. N Engl J Med. 2004;351:1187-96.

92. Shimazaki J, Higa K, Morito F, et al. Factors influencing outcomes 115. Inatomi T, Nakamura T, Koizumi N, et al: Midterm results on ocular
in cultivated limbal epithelial transplantation for chronic cicatricial surface reconstruction using cultivated autologous oral mucosal
ocular surface disorders. Am J Ophthalmol. 2007;143:945–53. epithelial transplantation. Am J Ophthalmol. 2006;141:267-75.

93. Baylis O, Figueiredo F, Henein C, et al. 13 Years of cultured limbal 116. Inatomi T, Nakamura T, Kojyo M, et al. Ocular Surface Reconstruction
epithelial cell therapy: a review of the outcomes. J Cell Biochem. With Combination of Cultivated Autologous Oral Mucosal Epithelial
2011;112:993–1002. Transplantation and Penetrating Keratoplasty. AJO. 2006;142:757-
64.
94. Jui-Fang Tsai R, Tseng SCG. Human Allograft Limbal Transplantation
for Corneal Surface Reconstruction. Cornea1994; 13(5): 389-400. 117. Ma DH, Kuo MT, Tsai YJ, et al. Transplantation of cultivated
oral mucosal epithelial cells for severe corneal burn. Eye (Lond).
95. Tan DTH, Ficker LA, Buckley RJ. Limbal transplantation. 2009;23(6):1442-50.
Ophthalmology 1996;103:29–36.
118. Uchino Y, Uchino M, Shimazaki J. Combination treatment of
96. Koizumi N, Inatomi T, Suzuki T, et al: Cultivated corneal epithelial intravenous immunoglobulin and cultivated oral mucosal epithelial
stem cell transplantation in ocular surface disorders. Ophthalmology transplantation for ocular cicatricial pemphigoid. BMJ Case Rep.
2001;108:1569-74. 2009; 2009: bcr09.2008.0979.

97. Koizumi N, Inatomi T, Suzuki T, et al: Cultivated corneal epithelial 119. Chen HCJ, Chen HL, Lai JY, et al. Persistence of transplanted oral
transplantation for ocular surface reconstruction in acute phase of mucosal epithelial cells in human cornea. Invest Ophthalmol Vis
Stevens-Johnson syndrome. Arch Ophthalmol. 2001;119:298-300. Sci. 2009 Oct;50(10):4660-8.

98. Shimazaki J, Aiba M, Goto E, et al: Transplantation of human limbal 120. Nakamura, T, Takeda K, Inatomi T, et al. Long-term results of
epithelium cultivated on amniotic membrane for the treatment of autologous cultivated oral mucosal epithelial transplantation in
severe ocular surface disorders. Ophthalmology 109:1285--90, the scar phase of severe ocular surface disorders. Br J Ophthalmol.
2002. 2011;95:942-6.

99. Nakamura T, Ishikawa F, Sonoda KH, et al: Characterization and 121. Satake Y, Higa K, Tsubota K, et al. Long-term Outcome of Cultivated
distribution of bone marrow-derived cells in mouse cornea. Invest Oral Mucosal Epithelial Sheet Transplantation in Treatment of Total
Ophthalmol Vis Sci. 46:497--503, 2005. Limbal Stem Cell Deficiency. Ophthalmology 2011;118:1524-30

100. Sangwan VS, Matalia HP, Vemuganti GK, et al. Early results 122. Takeda K, Nakamura T, Inatomi T, et al. Ocular surface
of penetrating keratoplasty after cultivated limbal epithelium reconstruction using the combination of autologous cultivated oral
transplantation. Arch Ophthalmol. 2005 Mar;123(3):334-40. mucosal epithelialtransplantation and eyelid surgery for severe
ocular surface disease. Am J Ophthalmol. 2011 Aug;152(2):195-20
101. Daya SM, Watson A, Sharpe JR, et al: Outcomes and DNA
analysis of ex vivo expanded stem cell allograft for ocular surface 123. Hirayama M, Satake Y, Higa K, Yamaguchi T, Shimazaki J.
reconstruction. Ophthalmology 112:470--7, 2005. Transplantation of cultivated oral mucosal epithelium prepared in
fibrin-coated culture dishes. Invest Ophthalmol Vis Sci. 2012 Mar
102. Shimazaki J, Higa K, Morito F, et al. Factors influencing outcomes 21;53(3):1602-9. doi: 10.1167/iovs.11-7847.
in cultivated limbal epithelial transplantation for chronic cicatricial
ocular surface disorders. Am J Ophthalmol. 2007;143:945–53. 124. Burillon C, Huot L, Justin V, et al.Cultured autologous oral mucosal
epithelial cell sheet (CAOMECS) transplantation for the treatment of
103. Ang LPK, Sotozono C, Koizumi N, et al. A Comparison Between corneallimbal epithelial stem cell deficiency. Invest Ophthalmol Vis
Cultivated and Conventional Limbal Stem Cell Transplantation for Sci. 2012 Mar 13;53(3):1325-31.
Stevens-Johnson Syndrome. Am J Ophthalmol. 2007;143:178–180.
125. Sotozono C, Inatomi T, Nakamura T, et al. Visual Improvement after
104. Meller D, Fuchsluger T, Pauklin M, Steuhl KP. Ocular surface Cultivated Oral Mucosal Epithelial Transplantation. Ophthalmology
reconstruction in graft-versus-host disease with HLA-identical living- 2013;120:193–200.
related allogeneic cultivatedlimbal epithelium after hematopoietic
stem cell transplantation from the same donor. Cornea 2009 126. Chan CC, Holland EJ. Infectious Keratitis After Boston Type 1
Feb;28(2):233-6. Keratoprosthesis Implantation. Cornea 2012;31:1128–1134.

105. Miri A, Al-Deiri B, Dua HS. Long-term Outcomes of Autolimbal and 127. Aldave AJ, Sangwan VS, Basu S, et al. International results with the
Allolimbal Transplants. Ophthalmology 2010;117:1207–13. Boston Type I keratoprosthesis. Ophthalmology 2012;119:1530–8.

106. Basu S, Fernandez MM, Das S, et al. Clinical outcomes of xeno-free 128. Jain R, Sangwan VS. Childhood bilateral limbal stem cell deficiency:
allogeneic cultivated limbal epithelial transplantation for bilateral long-term management and outcome. BMJ Case Rep. 2013 May
limbal stem cell deficiency. Br J Ophthalmol. 2012;96:1504–9. 29;2013. pii: bcr2013009508. doi: 10.1136/bcr-2013-009508.

107. Mannor GE, Mathers WD, Wolfley DE, Martinez JA. Hardpalate 129. Strampelli B. Nouvelle orientation biologique dans la ke ´ratoplastie.
mucosa graft in Stevens-Johnson Syndrome. Am J Ophthalmol. Bull Mem Soc Fr Ophthalmol. 1964;77:145–61.
1994;118:786–791.
130. Strampelli B, Valvo A, Tusa E. Osteo-odonto-cheratoprotesi in un
108. Fry TL, Wood CI. Readily available full-thickness mucous membrane caso trattato per anchiloblefaron e simblerafon totale. Ann Ottalmol
graft. Arch Otolaryngol Head Neck Surg. 1987;113:770–771. Clin Ocul.1965;91:462–79.

109. Naumann GO, Lang GK, Rummelt V, Wigand ME. Autologous 131. Strampelli B. Perfezionamenti technici della osteo-odonto
nasal mucosa transplantation in severe bilateral conjunctival mucus cheratoprosthesi. Ann Ottalmol. 1966;92:155–78.
deficiency syndrome. Ophthalmology 1990;97:1011–1017.
132. Strampelli B. Osteo-condro-cheratoprotesi in sostituzione della
110. Wenkel H, Rummelt V, Naumann GO. Long-term results after osteoodonto cheratoprotesi nei pazienti edentuli. Ann Ottalmol Clin
autologous nasal mucosal transplantation in severe mucus deficiency Ocul.1967;93:975-8.
syndromes. Br J Ophthalmol. 2000;84:279–284.
133. Strampelli B. Osteo-odonto-cheratoprotesi. AnInst Barraquer
111. Nakamura T, Endo K, Cooper LJ, et al. The successful culture and (Barc).1974;75:12–21.
autologous transplantation of rabbit oral mucosal epithelial cells on
amniotic membrane. Invest Ophthalmol Vis Sci. 2003;44:106–16. 134. Falcinelli GC, Missiroli A, Petitti V, et al. Osteo-odonto-
keratoprosthesis up-to-date. Acta XXV Concil Ophthalmol Milan.
112. Nakamura T, Inatomi T, Cooper LJ, et al. Phenotypic Investigation of 1987;2:2772–6.
Human Eyes with Transplanted Autologous Cultivated Oral Mucosal
Epithelial Sheets for Severe Ocular Surface Diseases. Ophthalmology 135. Falcinelli G, Falsini B, Taloni M, et al. Modified osteo-odonto-
2007;114:1080–8. keratoprosthesis for treatment of corneal blindness: long-term
anatomical and functional outcomes in 181 cases. Arch Ophthalmol.
113. Nakamura T, Inatomi T, Sotozono C, et al. Transplantation of 2005 Oct;123(10):1319-29.
cultivated autologous oral mucosal epithelial cells in patients with
severe ocular surface disorders. Br J Ophthalmol. 2004;88:1280–4.

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Ocular OScuurlafraScuerfaDceiDsoisrodrdeer

Mucous Membrane Vishnukant Ghonsikar
Graft MS, DNB,FICO,FAICO

Vishnukant Ghonsikar MS, DNB, FICO, FAICO, Neelam Pushker MD, M.S. Bajaj MD

Dr. Rajendra Prasad Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences, New Delhi

In ophthalmology mucous membrane graft (MMG) has to avoid damage to the parotid duct, whose opening is
unique application in reconstruction of ocular surface, opposite the upper second molar tooth, when harvesting
posterior lamella of lid, contracted socket and as a spacer for a buccal graft.
lid retraction. Today ophthalmologists are keen to explore Indications
these applications of MMG. Detailed knowledge about its • Ocular surface reconstruction e.g. symblepharon
various application, graft harvesting, surgical techniques &
postoperative care is very essential for providing successful release and reconstruction or excision and replacement
and safe outcome1,2. of keratinised conjunctiva in Steven Johnson’s
Grafts in lid reconstruction Syndrome (SJS).
Free grafts are often needed for large lid defects which • Lid reconstruction as posterior lamella
cannot be closed by direct suturing or advancement flaps. • Contracted socket
• For anterior lamella of the lid, full thickness skin grafts • As a spacer for lid retraction
• Severe eyelid cicatricial entropion
taken from ipsilateral or contralateral upper lid is the • Conjunctival replacement following an enucleation
best match. If enough upper lid skin is not available • With minor salivary gland in dry eye treatment
as in young patients, full thickness skin grafts can be Any patient who is to undergo an enucleation and who
taken from post auricular region, inner upper arm, has conjunctival scarring from previous surgery or trauma
supraclavicular region and nasolabial fold. may require a mucous membrane graft. The patient should
• For posterior lamella, tarsoconjunctival free graft is the be counseled about this possibility prior to surgery and
best option. Other options include buccal mucosa, the anesthetist should be informed. The anesthetist should
lip mucosa, nasal or hard palate mucoperichondrium, place a throat pack after induction of anesthesia and should
auricular cartilage. place the endotracheal tube to one side of the mouth. The
Mucous membrane graft [Lip/ Buccal mucosa]3 donor site is injected with xylocaine and adrenaline before
A mucous membrane graft can be removed free-hand or the patient is prepared and draped for surgery.
with the aid of a mucotome. It is generally easier and safer Hard palate graft4
to remove such a graft free hand. The donor sites are the Hard palate mucosa (Figure 2) is more rigid than lip or buccal
lower lip (Figure 1), upper lip, and the buccal mucosa. The mucosa as it has perichondrium. It has a rougher surface
lower lip is preferred. The access is easier and no sutures are because of keratinized epithelium unlike lip mucosa. It
required to close the donor site wound which epithelialises does not tend to shrink more than 10% postoperatively.
spontaneously over the course of 2 to 3 weeks. The buccal
mucosa yields more graft material but normally has to be
sutured and is not as accessible. Great care must be taken

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Ocular Surface Disorder 2 3
1

Figure 1: The mucous membrane graft is harvested
Figure 2: The area of the hard palate from which a graft can be safely harvested (shown with arrows)

Figure 3: Position of the nasal septal cartilage to be removed

Its use in upper eyelid should be avoided where it may Other Grafts
abrade the cornea except in the anophthalmic socket. The Auricular cartilage graft
anesthetist should place a throat pack after induction of The auricular cartilage graft has a number of indications
anesthesia. The donor site is injected with 3 to 5 ml of 0.5% but its use is limited by the anatomical size and shape of
Bupivacaine with adrenaline before the patient is prepared an individual patient’s pinna. In contrast to the hard palate
and draped for surgery. graft, the auricular cartilage graft has the disadvantage of
lacking a mucosal surface.
Indications Indications
• Spacer in lower lid retractor recession. • A tarsal replacement in upper eyelid reconstruction.
• Posterior lamellar graft in lower eyelid reconstruction. • A tarsal replacement in upper eyelid entropion surgery.
• Graft in severe lower eyelid cicatricial entropion • A tarsal replacement in lower eyelid reconstruction.
Nasal septal cartilage graft
surgery. A nasal septal cartilage graft (Figure 3) makes an
• Graft for the reconstruction of a contracted socket. ideal posterior lamellar replacement for lower eyelid
Upper eyelid tarso-conjunctival graft reconstruction where the whole of the lower eyelid has
A free tarso-conjunctival graft is harvested from the upper been resected. It is usually used in conjunction with a
eyelid. Caution should be exercised, however, in the use of Mustardé cheek rotation flap.
such a graft as the tarsus provides structural support for the Mucous Membrane Graft
upper eyelid and the adjacent conjunctiva. It is important A posterior lamellar mucous membrane graft is typically
to evert the upper eyelid preoperatively to ensure that the used for patients with a severe entropion with marked
height of the tarsus is adequate. A minimum of 3.5 mm of symblephara, severe lagophthalmos and eyelid retraction.
tarsus from the eyelid margin should be left undisturbed. A graft is indicated if the patient requires a subsequent
penetrating keratoplasty. Amniotic membrane may be used
Indications as an alternative graft if the patient agrees to the use of donor
• A posterior lamellar graft in eyelid reconstruction material. It is preferable to avoid the use of a hard palate
• A graft in severe upper or lower eyelid cicatricial

entropion surgery
• A spacer in lower lid retractor recession

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Ocular Surface Disorder

45

Figure 4: Extensive keratinization of posterior lamella of eyelid following severe Stevens–Johnson syndrome
Figure 5: Excision of the keratinized area avoiding damage to eyelashes

67

Figure 6: The lip mucosa has been marked and injected with local anaesthetic followed by careful
dissection for the removal of a mucous membrane graft

Figure 7: Observe for bleeders and if required bipolar cautery is used to cauterize any bleeding vessels

graft for use in the upper eyelid as the corneal surface, • The lower lip is everted with fingers or atraumatic
which is often already compromised, can be damaged by forceps. The lip mucosa is dried with a swab. The
its rougher surface. The procedure is usually performed template is transferred to the lower lip mucosa or
under appropriate anesthesia as per the patients age and the required lip mucosa is marked with avoiding the
co-operation. vermillion border and frenulum. This is outlined with a
sterile gentian violet.
Surgical steps
• The marked incision line is gently incised with a no.
For reconstruction of posterior lamella after 15 scalpel blade and the graft removed very carefully
symbhlepharon release in post SJS / Chemical injury using blunt-tipped Westcott scissors and small-toothed
• Two to three milliliters of bupivacaine with adrenaline forceps (Figure 6). The Westcott scissors should be
kept just under the surface of the graft with the edge of
mixed with lidocaine is injected along the upper lid the graft drawn horizontally to ensure that the graft is
skin crease. not inadvertently perforated and that the dissection is
• A 4/0 Silk traction suture or a cotton suture is placed not taken too deep. Dissection in a deeper plane risks
horizontally through upper eyelid margin centrally leaving areas of the lip with sensory loss.
and the eyelid is everted over a Desmarres retractor
(Figure 4). • The graft donor site is compressed with topical
• All symblephara are divided with Westcott scissors. adrenaline on a swab. Bipolar cautery is used to
• The conjunctiva at the upper border of the tarsus is cauterize any bleeding vessels (Figure 7).
incised and dissected free from all subconjunctival
scar tissue into the superior fornix and onto the bulbar • The graft is carefully shaped with Westcott scissors
surface of the globe (Figure 5). (Figure 8) and graft is then placed ensuring that the
• Next, a template is taken of the conjunctival defect or original graft surface faces upward, on the recipient
the size of the defect is measured. bed and interrupted 7/0 Vicryl sutures are placed
• The lower/upper lip mucosa is injected with local from the graft edge to the recipient conjunctival edge
anesthetic. (Figure 9).

• The graft must be maintained in position with the use of
a symblepharon ring when the graft is placed onto the

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Ocular Surface Disorder 9

8

Figure 8: The graft is carefully thinned with Westcott scissors removing any fibro-fatty tissue
Figure 9: The graft is then placed ensuring that the original smooth graft surface faces upward

10 References

Figure 10: The graft must be maintained 1. Brian Leatherbarrow: Oculoplastic Surgery Second Edition 2011.
in position with the use of full thickness Informa Healthcare Ltd.

anchoring sutures tied over pegs 2. Henderson HW, Collin JR. Mucous membrane grafting. Dev
Ophthalmol. 2008; 41: 230–42.
globe or a conformer of an appropriate size and shape
when the graft is placed centrally in an anophthalmic 3 . Putterman (1980): Basis oculoplastic surgery in Peyman GA:
socket. Principles and practice of ophthalmology, Vol. 3. Philadiphia: WB
• If the graft is used to reconstruct a conjunctival fornix Saunders Company, 2246-2333.
it should be held in place with a silicone retinal band
and 4/0 Nylon fornix-deepening sutures (Figure 10). 4. Bartley GB, Kay PP. Posterior lamellar eyelid reconstruction with a
• Topical antibiotic ointment is instilled into the eye. A hard palate mucosal graft. Am J Ophthalmol 1989; 107: 609–12.
compressive dressing is applied.
Postoperative Care of donor site
The patient is instructed to avoid any hot drinks or hot food
for a period of 1- 2 weeks. The patient is discharged on a
broad spectrum oral antibiotic for a week and an oral anti-
septic mouth wash for 2 weeks. Topical preservative free
antibiotic drops are instilled into the eye four times a day
for 2 weeks. A preservative free topical lubricant is used.
The patient is instructed to sleep with the head elevated for
1-2 weeks. The symblepharon ring is maintained in place
for a minimum period of 6 to 8 weeks. The patient has to
be reviewed twice weekly to ensure that the symblepharon
ring does not cause any corneal problems.

34 l DOS Times - Vol. 19, No. 4 October, 2013

Ocular OScuurlafraScuerfaDceiDsoisrodrdeer

Dry Eye Diagnosis and
Management Revisited

Rohit Shetty
DNB

Rohit Shetty DNB
Narayana Nethralaya, Bangalore, India

Dry eye disease is a major healthcare problem due to its • Cornea
increasing prevalence as well its impact on the quality • Temporal bulbar conjunctiva.
of life of patients, healthcare resources and the economy. Each zone is then given a score of ‘0’ (no stain) to ‘3’
It is now becoming evident that this previously under-
recognized condition should be regarded as a serious (confluent stain). Scores in each eye is totaled. A score of
public health problem that is worthy of prompt diagnosis 3.5 or greater indicates positive for keratoconjunctivitis
and effective treatment. Thorough evaluation is essential sicca. This test can give false negative results in mild or
to identify the type of dry eye and decide on the optimal very early cases of dry eye.
treatment for each patient. Lissamine green stains healthy epithelial cells not
In this article we will discuss the various clinical and protected by mucin (like Rose Bengal) and also
laboratory investigations currently in practice for the degenerated and dead cells (as in fluorescein). There
diagnosis of dry eye and introduce newer diagnostic is less discomfort and toxicity but the effect is too
modalities and also discuss the different treatment options transient to appreciate.
available for the management of dry eye. 4. Tear osmolarity – A hand drawn micropipette or
Diagnosis 0.2 microlitre microcap is used to collect 0.1 to 0.2
1. Tear film break up time (BUT) – microlitre of tear from the inferior marginal tear strip
BUT is the time interval between the last blink and by capillary action taking care not to touch the ocular
surface, and tested directly on the Osmometer. The
appearance of randomly distributed dry spots in a normal tear osmolarity is approximately 302 mOsm/L.
flourescein stained tear film. < 6 seconds - suggests A reference or cut off value of approximately 312
evaporative dry eye. mOsm/L is indicative of pathology.
2. Schirmer’s test: Test with topical anaesthesia is more 5. LipiView ocular surface interferometer1– (Figure 1)
reliable in clinical practice. PRINCIPLE – white light interferometry
Inference - > 15 mm - normal, 6 to 10 mm - borderline • Provides an interferometry colour assessment of
dry, < 6 mm - impaired secretion.
3. Rose Bengal staining – The dye has an affinity for dead the tear film by specular reflection
or devitalized epithelial cells and for areas devoid of • Measured in interferometric colour units (ICU)
mucus.
Van Bijsterveld scoring system – divide the ocular (Figure 2).
surface into three zones: • ICU is the colour scale resulting from the
• Nasal bulbar conjunctiva.
interference pattern which occurs at the boundary
of the tear film.
• LipiView uses advanced interferometric technology
and captures detailed digital images of the eye’s

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Ocular Surface Disorder

Figure 1: LipiView Interferometer Figure 2: LipiView

Figure 3: Normal meibomian glands Figure 4: Meibomian gland atrophy in
chronic meibomian gland Dysfunction

tear film to assess the oily lipid layer of tear film c) Measurement of tear meniscus height using
(Figure 3). calipers (Figure 6).
• LipiView ≤ 70 is considered abnormal (Figure 4).
6. Keratograph: Used for the assessment of corneal d) Evaluating the particle flow characteristics - A
topography and dry eye evaluation. Incorporated with video recording with up to 32 images per second
white diodes for the assessment of tear film particles enables the observation of the tear film particle flow
movement, blue diodes for fluorescein imaging, characteristics and shows the tear film viscosity.
infrared diodes for meibography.
a) Meibography2 - shows the morphological changes 7. Meibomian gland evaluation - Performed with the help
in the glandular tissue. of a meibomian gland evaluator which is a hand-held
b) Non invasive keratograph break up time (NIKBUT) tool used for evaluating meibomian gland secretions.
– maps the tear film break up time (Figure 5). It is designed to deliver consistent gentle pressure,
through the eyelid, to the meibomian glands, to
mimic the forces of a deliberate blink and to express
meibomian secretions. The evaluator is placed onto

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Ocular Surface Disorder

Figure 5: Non invasive keratograph break up time Figure 6: Tear film height measurement

the outer lid skin immediately below the lash line and Figure 7: Meibomian gland evaluator
depressed about half way and its position adjusted
so that a clear view of the meibomian gland orifices Treatment
is obtained. Documentation is done as to how many Delphi panel consensus for dry eye management
meibomian glands yield liquid secretion during the A. Supportive measures
expression. A total score of < 4 glands secreting • Use of room humidifiers.
clear oil is considered to be a significant blockage of • Avoid extreme/harsh environmental conditions.
meibomian gland orifices (Figures 7,8,9,10). • Avoid drugs causing dry eye.
8. Tear film cytokines:3,4 Increased levels of inflammatory • Moist chamber spectacles.
mediators in tears like interleukin (IL)-6,4,10, • Contact lens.
interferon ¡ (INF ¡), tumour necrosis factor factor a B. Medical management
(TNF a) - proves the inflammatory pathology in dry 1. Artificial tear substitutes (prefer preservative free)5 - to
eye. Increased inflammatory mediators are seen with
increasing severity of dry eye. This makes the basis for be used regularly and frequently (Table 1).
anti-inflammatory therapy in dry eye. • Dose: hourly in severe dry eyes. 4-6 times a day in
9. Other tests:
a. Lysosyme assay – normal 1-3mg/ml. Decreased in moderate cases. Preservative free drops should be
used to prevent epithelial toxicity.
dry eye disease. • Provides only temporary relief and have not been
b. Lactoferrin - normal 2-3mg/ml - has significant found to reverse conjunctival squamous metaplasia

antibacterial activity – measured by lactocard
solid phase Enzyme Linked Immunosorbent
Assay (ELISA) technique. Decreased in Sjogren’s
syndrome.
c. Conjunctival impression cytology -
• To do quantitative measurement of goblet

cells & qualitative assessment of epithelial
morphology.
• To monitor progression of ocular surface
change.
• Nitrocellulose membrane is pressed against
bulbar or tarsal conjunctival surface. Three
features are observed namely loss of goblet
cells, increased nucleo-cytoplasmic ratio and
keratinization.

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Ocular Surface Disorder

Figure 8: Normal meibomian gland secretions Figure 9: Meibomian gland secretions in
Meibomian gland disease (MGD)

Figure 10: Meibomian gland evaluation grading
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Ocular Surface Disorder

Table 1: Tear substitutes Properties 8. Newer treatment modalities -
Polymer Increases the viscosity of • Ocular inserts6 -
Cellulose esters tears • Cylindrical rod containing 5mg Hydroxypropyl
(Hyperomellose 0.3-1%, Closely resembles natural
Hydroxyethylcellulose, tears methyl cellulose (HPMC) placed in the lower cul-
Methylcellulose 0.1-1%, de-sac.
Carboxymethylcellulose) Optimal wetting properties • Imbibes fluid and swells
Polyvinyl alcohol at 1.4% • Lasts for 12 -24 hrs
Povidone 0.6% Superior wetting when co- • Secretagogues
formulated with polyvinyl • Stimulate endogenous tear production
Carbomers (polyacrylic alcohol • Oral pilocarpine (Salagen) 5mg four times a day7 –
acid) High molecular polymers of cholinergic side effects.
acrylic acid • Cevilemine – Fewer side effects.
Hyaluronic acid, High viscosity when eye is
Chondroitin sulfate 0.1% static, shears and thins with • Mucolytic agents as acetylcysteine 5% drops used in
eye movement and blinks patients with corneal filaments and mucous plaques.
Increased retention when
combined with polyvinyl • Autologous serum drops [diluted 1:3 with saline] have
alcohol reported to reduce ocular irritation and conjuntival and
Glycosaminoglycan corneal dye staining in Sjogren’s syndrome associated
disaccharide biopolymers aqueous tear deficiency.
Long retention times
C. Surgical management
• Contains: 1. Lateral tarsorrhaphy- reduces evaporation of tears
• Polymer and preservative
• 0.9% NaCl for tonicity by decreasing the exposed surface area in the
• Buffers like boric acid interpalpebral fissure.
2. Gels (carbomers) require less frequent application than 2. Punctal plugs8 - (temporary)
• Description
drops. • Placement of a silicone or collagen plug into the
3. Ointments using petrolatum, lanolin and mineral oil
punctum to prevent tears from draining out of the
base, dissolve at the temperature of ocular tissue, eyes and into the nose through the lacrimal duct.
retained in the cul-de-sac for long - used mainly at • Correct size plug is selected by the practitioner and
night time. inserted either with or without punctal dilation.
4. Tetracyclines are used for meibomitis. • Indication - Moderate dry eye that is unresponsive to
5. Anti-inflammatory agents -As artificial tears do not drug therapy
directly inhibit the ocular surface inflammation in dry • Complications
eyes, anti inflammatory therapy has to be considered • Epiphora (excessive tearing) in some patients due
for patients with: to less punctal drainage (early).
• A stagnant and unstable tear film who continue to • Possible chronic epiphora if the plug is lost in
the canaliculus; dacryocystorhinostomy could be
have symptoms that are not relieved by artificial required to restore the patency of lacrimal drainage
tears. system (late).
• Corneal epithelial disease. 3. Punctal cautery - (permanent)
• Drug used is - Cyclosporine 0.05%-0.1% - two to • Description
four times a day. • Cautery is applied directly to the punctum to
6. Botulinum toxin injection is given in lagophthalmos, destroy the drainage pathways of tears out of the
eyelid retraction, exposure and neurotrophic eyes and into the nose.
keratopathy. • Local anesthetic may be used.
7. Soft contact lens to be used in conjunction with tear • Indication - Chronic, severe dry eye that has not
substitutes. improved by lubricants or cyclosporine. Usually, these

www. dosonline.org l 39

Ocular Surface Disorder

Figure 11: Lipiflow procedure - screenshot • Mucous membrane graft (current gold standard
as it has its own epithelium).
Figure 12: Lipiflow lid warmer and eye cup
• Amniotic membrane graft.
patients would have had punctal plugs that routinely • Limbal stem cell graft.
fall out of the punctum, requiring regular replacement • Meibomian gland dysfunction - warm compresses,
by new plugs.
• Complications lid massage, lubricants, topical and oral
• Infection (rare) tetracyclines.
• Epiphora 6. Newer treatment modality: Lipiflow Thermal Pulsation
4. Salivary gland transplant9 - in cases of severe dry eye, System10 (Figure 11,12).
transplantation of minor salivary glands or the parotid
duct. • Application of localized heat and pressure therapy
5. Treatment of associated conditions in patients with meibomian gland dysfunction
• Blepharitis - Adequate lid hygiene and antibiotic (evaporative or lipid deficiency dry eye).

therapy. • Provides controlled, outward directional heat and
• Eyelid malpositions like entropion, ectropion due intermittent pressure therapy to eyelids to facilitate
release of lipid from the cystic meibomian glands.
to aging, eyelid scarring in ocular surface disease
and congenital malformations to be treated. Summary
• Ocular surface reconstruction - In Stevens Johnson Step 1. Evaluation of symptoms and also ask for history of
syndrome, Ocular cicatricial pemphigoid, any other systemic disease, allergic status, duration and
chemical or thermal burns using: change in symptoms with day progression, environment,
and seasons.
Step 2. Make sure to rule out meibomian gland duct
obstruction or dysfunction, and any significant lid or ocular
pathology.
Step 3. Perform the investigations and interpret results so as
to reach the right diagnosis and estimate severity of disease.
Step 4. Decide the line of treatment.

References

1. Blackie CA et al. The relationship between dry eye symptoms and
lipid layer thickness. Cornea 2009;28(7):789-94.

2. Ban Y et al. Morphological evaluation of meibomian glands using
noncontact infrared meibography. Ocul Surf. 2013;11(1):47-53.

3. Sambursky R, Davitt WF, Latkany R, et al. Sensitivity and specificity
of a point-of-care matrix metalloproteinase 9 immunoassay for
diagnosing inflammation related to dry eye. JAMA Ophthalmol.
2013; 131(1); 24-8.

4. Tong L et al. Association of tear proteins with Meibomian gland
disease and dry eye symptoms. Br J Ophthalmol. 2011;95(6):848-52

5. Doughty MJ, Glavin S. Efficacy of different dry eye treatments with
artificial tears or ocular lubricants: a systematic review. Ophthalmic
Physiol Opt. 2009;29:573-83.

6. Koffler B, McDonald M, Nelinson D, LAC-07-01 Study Group.
Improved signs, symptoms, and quality of life associated with dry
eye syndrome: hydroxypropyl cellulose ophthalmic insert patient
registry. Eye Contact Lens 2010;36:170-6 .

7. Ibrahim OM et al. Visante optical coherence tomography and tear
function test evaluation of cholinergic treatment response in patients
with sjögren syndrome. Cornea 2013;32(5):653-7.

8. Ervin A, Wojciechowski R, Schein O. Punctal occlusion for dry eye
syndrome. Cochrane Database Syst Rev. 2010;8:CD006775.

9. Ge XY et al. An experimental study of the management of
severe keratoconjunctivitis sicca with autologous reduced-sized
submandibular gland transplantation. Br J Oral Maxillofac Surg.
2012 Sep;50(6):562-6.

10. Lane SS et al. A new system, the LipiFlow, for the treatment of
meibomian gland dysfunction. Cornea 2012;31(4):396-404.

40 l DOS Times - Vol. 19, No. 4 October, 2013

Ocular OScuurlafraScuerfaDceiDsoisrodrdeer

Allergic Conjunctivitis– Bithi Chaudhary
A Review MS, FRCS

Bithi Chowdhury MS, FRCS
NDMC Medical College and Hindu Rao Hospital, Delhi

Ocular allergy is one of the most common ocular Pathophysiology
conditions encountered in clinical practice. Ocular The response to allergen in allergic conjunctivitis is due to
allergy is estimated to affect 5 – 22% of the population its interaction with prostaglandins and leukotrienes. It is a
depending on the geographical setting and the age of type I hypersensitivity reaction and the early response lasts
the population1. It is also often under diagnosed and clinically for 20 -30 minutes. The late phase reaction is due
undertreated. Definitive etiology is not known but genetic to the presence of inflammatory cells in the conjunctival
predisposition, air pollution in urban area and exposure mucosa. This is brought about by activation of vascular
to pets have been associated. Besides causing irritating endothelial cells, which in turn expresses chemokines,
symptoms, visual loss in severe cases, its effect on the quality adhesion molecules such as such as intercellular adhesion
of life and economic burden on the patient is profound. molecule (ICAM) and vascular cell adhesion molecule
This article broadly outlines the clinical features, diagnosis, (VCAM). Other chemokines secreted include regulated
investigation and treatment of allergic conjunctivitis. upon activation normal T cell expressed and secreted
Types of allergic conjunctivitis (RANTES) chemokines, monocyte chemo attractant
Seasonal allergic conjunctivitis (SAC) and perineal allergic protein (MCP), interleukin (IL)-8, eotaxin and macrophage
conjunctivitis (PAC) are the most commonly seen allergic inflammatory protein (MIP)-1 alpha.
conjunctivitis. Atopic keratoconjunctivitis (AKC), vernal
keratoconjunctivitis (VKC), giant papillary conjunctivitis Clinical features
(GPC) and contact dermatitis conjunctivitis (CDC) The clinical presentation in both the conditions is similar.
represents the other spectrum of the disorder. Patients complains of bilateral itching, tearing and burning
GPC is caused by micro trauma especially with the use sensation. Blurred vision and photophobia may be due
of extended wear soft contact lens. Those with history to an alteration in the composition and instability of the
of allergy have high risk of having GPC. CDC belongs tear film. PAC affects young adults between 20-40 years
to a different category of allergic reaction as it is not IgE of age with no gender predilection while SAC has no age
mediated. or gender predilection. Both are frequently associated with
Seasonal Allergic Conjunctivitis and Perineal allergic rhinitis and other allergic disorder (slightly more
Allergic Conjunctivitis with SAC). On examination, mild to moderate conjunctival
SAC is the most common form of all ocular allergic diseases hyperemia with an edematous conjunctival surface is seen.
and is triggered by exposure to pollen. It usually occurs in The palpebral conjunctiva appears pale pink in color with
spring. PAC is induced by exposure to dust mites fungi, diffuse areas of slightly hypertrophic papillae predominantly
animal epithelial and/or occupational allergens. The located in the upper tarsal conjunctiva (Figure-1a,b). The
affected patients can show symptoms throughout the year cornea is rarely affected.
with acute seasonal exacerbations. Diagnosis: Diagnostic features of SAC and PAC consist of
itching, redness, and swelling of the conjunctiva. However
other criterias that help in the diagnosis are a family

www. dosonline.org l 41

Ocular Surface Disorder Th2 subpopulation) would take place. There is abundant
mucosal secretion in these individuals due to increased
Figure 1a: Conjunctival hyperemia and edema presence of goblet cells in the conjunctiva.
Clinical features
The disease presents with itching, redness, photophobia
and watering. The symptoms may be seasonal or perennial
with exacerbations in heat, dust, wind, bright light. Two
forms of conjunctival involvement is known: palpebral,
with giant subtarsal papillae (>1 mm in diameter) showing
a typical cobblestone pattern with profuse mucus secretion
(Figure 2) and limbal with Horner-Trantas dots that appear
as small gelatinous nodules at limbus and are typical of the
active phase of the disease (Figure 3).
Corneal involvement can manifest as a micropannus
superficial punctate keratopathy (normally located in the
upper half of the cornea), corneal macro erosions and
shield ulcerations (occurs in 3%-11% of cases) covered
with mucus and fibrin plaques (Figure 4), subepithelial
scarring and pseudogerontoxon. VKC is strongly associated
with keratoconus, hydrops and may cause dry eye.

Figure 1(b): Papillary hypertrophy Figure 2: Giant papillary hypertrophy
Figure 3: Horner Trantas dots
or personal history of atopy and skin test, response to
antiallergic treatment, serum IgE elevation (found in 78%
of all patients with SAC–69% being specific of pollen),
lacrimal IgE elevation (in 96% of the patients), increased
mast cell infiltration of the conjunctiva (in 61% of the cases)
and increase in type T mast cells with tryptase release in
tears.
Vernal keratoconjunctivitis
VKC is a self-limiting, bilateral chronic inflammation that
leaves sequelae or permanent alterations in visual acuity
in about 5-6% of the patients. It is more frequent in young
males with an increased incidence between 11-13 years of
age. VKC is rare in adults.
Pathophysiology is not precisely known, though two
hypersensitivity mechanisms seem to be involved
(type I and type IV). Accordingly, in the presence of an
antigen, lymphocyte activation (predominantly of the

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Figure 4: Shield ulcer Loss of lashes due to scratching results in “Hertoghe
sign”. Lid margins may have staphylococcal blephritis,
Figure 5: Atopic Keratoconjunctivitis mebomitis, trichiasis, entropion and ectropion. Papillary
hypertrophy is predominantly seen in lower palpebral
Diagnosis conjunctiva and symblephron formation and conjunctival
Diagnosis is based on typical signs and symptoms. Large scarring occurs in chronic cases. Corneal involvement is
papillae in the upper tarsal conjunctiva and corneoscleral in the form of superficial puctate keratitis, ulcer formation,
junction are hallmark of VKC. Conjunctival biopsy reveals neovascularisation, pannus formation and rarely Horner
an increase in basophils, eosinophils, mast cells, plasma Trantas dot. These eyes are prone to herpetic and fungal
cells and lymphocytes that also appear in the smears. The keratitis. These patients also develop atopic cataracts
tears show very high levels of histamine, tryptase, eotaxin which are anterior shield like cataracts (Figure 6). There
and eosinophil cationic protein and increased adhesion is increased association of keratoconus and retinal
molecules (VCAM-1) and leukotrienes (LTB4, LTC4). detachment with AKC.
Atopic keratoconjunctivitis Diagnosis
It is a bilateral chronic inflammatory disease affecting the It is done mainly by history and clinical examination. A
eyelids and ocular surface in young males with atopic conjunctival biopsy is sometimes needed to differentiate it
disease. from other forms of cicatrizing conjunctivitis.
Pathophysiology Giant papillary conjunctivitis
It involves type I and type IV hypersensitivity reaction with GPC is non-infectious inflammatory disorder of the surface
activation of Th1 and Th2 lymphocytes and reduction of of the eye, related to the wearing of contact lenses, ocular
MU5CAC secreting goblet cells. prostheses, sutures and even limbal dermoids. The disorder
Clinical features affects 5-10% of all contact lens wearers and is more common
Patients complain of itching, redness, swelling and among individuals wearing soft lenses. GPC can manifest
eczema of eyelids. Chronic edema of lower lid causes at any age and shows no race or gender predilection. It can
“Dennie – Morgan fold” at infraorbital area (Figure 5). affect both atopic and non-atopic individuals, though the
signs and symptoms are more severe among the former.
Etiopathogenesis
Mechanical trauma to the conjunctiva and cornea causes
release of local inflammatory mediators such as IL-8 and

Figure 6: Atopic Cataract

www. dosonline.org l 43

Ocular Surface Disorder

Table 1: Differentiating features of various allergic conjunctivitis2,3,4

Features SAC PAC VKC AKC GPC CDC
Constant Possible Possible
History of Common Common Possible Adolescent/adults adults
atopy Children/adults No predilection No
Spring predilection
Age Children/ Children/adults Children/adults Males No no
Adults Minimal no
Perennial >1 Minimal
Gender No No Males no
predilection predilection Yes Edema
Severe No Dermatitis
Seasonal Spring Perennial Perennial/ <1 Yes yes
summer Variable No
Dermatitis Not frequent Variable
Cornea No no Yes Not frequent
No Variable
Vision Minimal Minimal Mild Variable Variable
No Variable Variable
Papillary No no 7-8mm Variable
hypertrophy Limbus Greatly Variable
affected elevated No
Characteristic Constant
Periocular skin Edema Edema Edema Constant
involvement Decreased
Positive
Exposure to No no No Asthma
drugs Rhinitis
Dermatitis
Contact lens No No No Low
use
Constant
Serum IgE elevated elevated Variable

Eosinophils in Frequent Very frequent Characteristic
conjunctival
swab Increased Increased Incresed
Goblet cells Positive Positive Nonspecific
Skin test Asthma Asthma Variable
Other atopic Rhinitis Rhinitis
disease

Response to Yes Yes Low
antiallergic Constant Constant Constant
drugs
Response to
steroid

the recruitment of dendritic cells which increase antigen the spring season. Dry eye and genetic predisposition may
presentation to the cells. Bacterial products, lubricating be contributary. Patients present with increase in contact
eyedrops, preservative solutions, disinfecting solutions, lens soilage, ocular itching and mucous discharge in tears
and even the contact lens material itself can act as the as well as blurred vision and conjunctival injection. This
antigenic stimuli. Increased contact lens water content and can be accompanied by decreased contact lens tolerance
thicker and more irregular lens margins are correlated to an and mechanical stability. Examination of the superior
increased frequency of the disease. tarsal conjunctiva reveals giant papillae measuring over
Clinical features 1 mm in size. Corneal involvement can be in the form
The disease is seen in any age with no race or gender of punctate keratitis, peripheral infiltrates and corneal
predilection. Exacerbations are usually observed during neovascularisation.
Diagnosis is by history and clinical examination

44 l DOS Times - Vol. 19, No. 4 October, 2013

Ocular Surface Disorder

Table 2: Drugs used in allergic diseases of the eye

Name Mode of action Effect Examples Indication Dosage Adverse effect
Antazoline, PAC, SAC Tds to Irritation
Antihistamines Blocks the action Relieves itching Pheniramine, qid especially on
of histamine by and redness Levocabastine PAC, SAC prolonged use
blocking the (0.5%)
histamine receptors Oxymetazoline,
Naphazoline,
Vasoconstrictor Constricts blood Decongestion Tetrahy- Tds Burning, stinging,
vessels drozoline, mydriasis,
Phenylephrine rebound
hyperemia
Mast cell Influx of calcium Used for Sodium PAC, SAC conjunctivitis
stabiliser into mast cell prophylaxis cromoglycate, medicamentosa
Multiple action decreases Lodoxamine with chronic use
drugs degranulation which Relieves itching,
decrease the release redness, edema Tds Require loading
NSAID (non of histamine and with immediate period before
steroidal anti chemotactic factors effect exposure to
inflammatory Exert multiple antigen hence
drugs) pharmacological Reduce the requires very good
Corticosteroids effects such as conjunctival compliance
histamine receptor hyperemia and
antagonist action, the pruritus Olopatadine PAC, SAC, Bd Blurred vision,
stabilization of mast caused by (0.1%) Ketotifen VKC, AKC, burning and
cell degranulation lukotrienes and (0.025%), stinging
and suppression prostaglandins Nedocromil,
of activation and Used in severe Azelastine,
infiltration of and chronic Epinastine
eosinophils forms, relieves (0.05%)
Block all signs and
cyclooxygenese symptoms. Ketorolac SAC, VKC Tds Burning and
pathway, reduces (0.5%), stinging
prostaglandin Pranoprofen,
and thromboxane Fluribuprofen, Tds Cataract,
synthesis Diclofenac glaucoma,
(0.1%) infections,
Interfere with delayed wound
intracellular protein Medroxy- Severe healing
synthesis and block progesterone, forms of
phospholipase A2. Fluormetholone, all allergic
They also inhibit Dexamethasone conjunc-
cytokine production (0.1%), tivitis
and inflammatory Prednisolone for short
cell migration (1%), duration
Clobetasone,
Rimexolone,
Loteprednol,
(.02% & .05%),
Subtenons
injection of
triamcinalone
acetonide

contd...

www. dosonline.org l 45

Ocular Surface Disorder

Name Mode of action Effect Examples Indication Dosage Adverse effect
Immuno- AKC, VKC Tds Burning, ocular
supressives Cyclosporine Decreases Cyclosporins
inhibits eosinophil steroid dosage (1%; 2%), pain
Oral infiltration by and tacrolimus is Tacrolimus
antihistamines affecting type IV useful in steroid (0.003%)
hypersensitivity resistant cases
reaction. Tacrolimus
acts by inhibiting the
action of T-cells.

These block H1 Reduces Cetirizine, Severe Od;bd Dry eye especially
receptors some have itching,edema Loratadine, allergic with second
anti-inflammatory vasodilatation in Ebastine, conditions generation
properties by severe allergic Levocetirizine, antihistamines.
inhibiting ICAM1 conjunctivitis. Fexofenadine
and PGF.

Od: Once a day; Bd: two time a day; Tds: Three time a day; qid: four time a day

Contact dermatitis allergy Figure 7: Contact Dermatitis Conjunctivitis
It is a type IV mediated hypersensitivity response that
involves interaction of antigen with Th1 and Th2 cells Differentiating features of various types of allergic
resulting in release of cytokines. conjunctivitis in the form of epidemiology, history, clinical
features and response to treatment are summarised in
Pathophysiology (Table 1) (adapted from Mantelli et al.)
Typically, it consists of two phases: sensitization and Treatment of allergic conjunctivitis
inflammatory response. In the sensitization phase antigen A. Medical5
presenting cells processed antigen - MHC class II complex The mainstay of treatment is anti allergic drugs. These
interacts with T-lymphocytes, resulting in the differentiation include antihistamine, vasoconstrictors, mast cell
of CD4+ T-lymphocyte into memory T-lymphocyte. In stabilisers, dual mode action drugs, corticosteroids and
the second phase, the interaction between the antigen- immunosuppressives. The regimen that is usually followed is
MHC-II complex and memory T-cells stimulates the as follows: In mild cases, antihistamines or vasoconstrictors
proliferation of T-cells. The memory T-lymphocytes suffice. In moderate cases, NSAID is added along with dual
during proliferation release cytokines. In sensitized action drugs. In severe cases, steroid drop are given for a
individuals, the immune response takes 48-72 hours to short duration of upto 2 weeks followed by dual action drugs.
develop. Some of the products that can act as antigens Duration of treatment depends on patients response and
are: mydriatic drugs (atropine, homatropine, tropicamide, the nature of the allergy. Mast cell stabilisers are given prior
phenyephrine); antiglaucoma drugs (Brimonidine, to the onset of symptoms in susceptible cases. Cyclosporins
apraclonidine dorzolamide); preservatives (thiomersal, and tacrolimus is used in severe cases of VKC and AKC.
benzalkoniumchloride, chlorhexidine EDTA); antibiotics Allergen-specific immunotherapy is an effective treatment
(aminoglycosides, sulfamides, polymyxin); antiviral drugs for patients with allergic rhinoconjunctivitis. The drugs,
(idoxuridine, trifuridine, viderabine); anaesthetic agents their mechanism of action, dosage and adverse effects used
(procaine, tetracaine); cosmetics, soaps and detergents. in various allergic conjunctivitis are summarised in table 2

Clinical features
The lower palpebral conjunctiva is involved first followed
by rest of the conjunctiva. The eyelids may show blephritis,
eczematous dermatitis which later resulting in folds, crusts,
fissures, and skin thickening (Figure 7). The conjunctiva
shows follicles, papillae, psedopemphigoid lesions. Corneal
involvement may be in the form of superficial punctuate
keratitis, marginal infiltrate, ulcer and stromal edema.
Diagnosis is by history and clinical examination

46 l DOS Times - Vol. 19, No. 4 October, 2013

Ocular Surface Disorder

B. Supportive References

Supportive therapy includes artificial tears, goggles and 1. Mario La Rosa, Elena Lionetti, Michele Reibaldi, et al. Allergic
cold eye pads. Artificial tears dilulte the concentration of conjunctivitis: a comprehensive review of the literature Italian
allergens and inflammatory mediators and flush the ocular Journal of Pediatrics 2013, 39:18.
surface of these agents. Goggles decrease the amount of
allergen reaching the ocular surface while cold eye pads 2. Mantelli F, Lambiase A, Bonini S. A simple and rapid diagnostic
offer for symptomatic relief. Avoidance of allergen should algorithm for the detection of ocular allergic diseases. Curr Opin
be tried wherever possible. Allergy Clin Immunol. 2009; 9(5):471-76.

C. Surgical 3. Kumar S: Vernal keratoconjunctivitis: a major review. Acta
Ophthalmol. 2009, 87:133-147.
Surgical treatment may be required in severe cases of AKC
and VKC. Surgical excision, cryocoagulation, excision 4. MC Sánchez, B Fernández Parra, V Matheu, et al. (SEAIC
with Mitomycin C 0.02% or COof2 laser is used for papillary Rhinoconjuntivitis Committee 2010). Allergic Conjunctivitis. J
hypertrophy. Debridement ulcer base/surgical or Investig Allergol Clin Immunol. 2011; Vol. 21, Suppl. 2: 1-19

5. Gyan P Mishra, Viral Tamboli, Jwala Jwala, Ashim K Mitra-
Recent patents and emerging therapeutics in the treatment of
allergic conjunctivitis. Recent Pat Inflamm Allergy Drug Discov.
2011;5(1)26-36.

excimer laser keratectomy, amniotic membrane graft/free
autologous conjunctival graft are the various options for
managing non healing shield ulcer. Tarsal plate resection
is done for mechanical ptosis.

www. dosonline.org l 47

DiaDginagonsotsitcicss

Corneal Topography

Aditi Manudhane
MS

Aditi Manudhane MS, Ritu Arora MD, DNB, J.L.Goyal MD, DNB,
Parul Jain MS, Gaurav Goyal MS
Guru Nanak Eye Centre, New Delhi

The cornea is the most important refractive element of data are directly calculated from the elevation data without
the human eye, providing approximately two thirds approximations3.
of its optical power. Detailed examination of the corneal Rasterphotogrammetry: The PAR Corneal Topography
curvature is an essential part of the workup before refractive System was the first topography system to produce an
surgery1, for fitting of contact lens and for diagnosis and elevation map of the corneal surface4. The system projects a
management of ectatic disorders. Keratometry was one grid onto the corneal surface after instillation of fluorescein.
of the earliest methods for measuring corneal shape. Distortions in grid patterns are analysed to determine
However, it gives limited information about corneal shape corneal elevation based on camera and grid projection
and appreciates only gross amount of astigmatism. These angles. Eg- Euclid ET-800 (Euclid Systems corp.,NJ)
limitations led to the development of more advanced Scanning Slit Imaging: The Orbtek Orbscan is based on
techniques for evaluating corneal shape. the innovative principle of measuring the dimensions of a
Three types of systems are used to measure corneal slit-scanning beam projected on the cornea. Using slit or
topography: Placido based, elevation based and parallelopiped methodology, the curvature of the anterior
interferometric. Recently Scheimpflug imaging has become and posterior surface of the cornea can be assessed along
increasingly popular. with the anterior surface of the lens and iris. During the
Placido based systems: The handheld Klein keratoscope and examination, the patient fixes on a light source, whose reflex
Placido disc enable observation of reflections of multiple is aligned with the instrument axis. Two scanning slit lamps
concentric circles from the corneal surface. The reflective project a series of 40 (20 from the left and 20 from the right)
mires appear closer together on steeper parts of the cornea slit beams angled at 45 degrees to the right and left of the
and farther apart in flatter areas. Localized changes, such as video axis. A “tracking system” attempts to minimize the
tight sutures after a corneal transplant, will cause distortion influence of involuntary eye movement. The instrument’s
of the mires in the area of suture compression. Currently software analyzes 240 data points per slit (total 9600 points)
available videokeratoscopes are- Eye MapEH -290 (Alcon), and calculates the corneal thickness and posterior surface
EMS (Zeiss) and Keraton Videokeratoscope (Optikon). of the entire cornea. Total duration of examination is 1.5
Limitations of the placido based system are: seconds. The newer version, Orbscan II (Orbtek, Inc.)5
o Difficulty to acquire data points within the central 2 incorporates a Placido-disk attachment to obtain curvature
measurements directly. Thus, Orbscan II has the benefits of
mm of the cornea both placido-disc and slit scanning approaches of corneal
o Imaging objects with sudden slope transitions, topography. The most recent hardware upgrade is the
Orbscan IIz with version 3.12 software. It is integrated with
alignment, focusing or centration errors. a Shack-Hartmann aberrometer in the Zyoptix workstation
Elevation Based Systems: This method enables for evaluating patients of refractive surgery.
measurement of both anterior and posterior corneal
surface2. Currently, two systems measure corneal elevation Interpretation of corneal topography (Table 1,2)
directly: PAR Corneal Topography System (CTS; PAR Corneal topography is analysed using colour coded
Vision Systems Corp., New Hartford, NY) and Accugrid contour maps of corneal power with cool colours (green,
and Orbtek Orbscan (Bausch and Lomb). The curvature blue) representing lower corneal powers and warm colours
(orange, red) representing high corneal powers.

www. dosonline.org l 49

Diagnostics

Table 1 Table 2: Numerical and Statistical indices7

Absolute scale6 Normalised scale6 Simulated Keratometry Maximum power of the surface
(Sim K) along any axis and the power
Preset colour scale with Different color scales orthogonal to that axis (Sim K1
same diopteric steps. assigned to each map. & Sim K2)

Minimum and maximum Instrument identifies actual Mean values at central Mean value at central 3 mm
assigned to same colours minimal and maximal zone

keratometric dioptric value Surface regularity • Measures regularity in central
of a particular cornea. index(SRI) 4.5 mm
• Calculated from local power
Larger increment in steps Range assigned to each fluctuations along 256 equally
(0.5 D), so may miss subtle colour is smaller, therefore spaced meridians on 10 central
changes. it gives a more detailed mires.
description. • Zero for smooth surface,
increases with increasing
Curvature/power map astigmatism.
Axial curvature/sagittal curvature: It is calculated by
measuring the perpendicular distance from the tangent at a Surface asymmetry Weighted summation of
point to the sagittal (optical) axis. Index (SAI) differences in corneal power
Meridional curvature/tangential and instantaneous between corresponding points
curvature - Tangential radius of curvature is calculated at 180 degree apart.
each point with respect to its neighboring points by fitting 0 for a perfect sphere
the best-fit sphere (BFS). It gives better representation of
local irregularity, than axial radius of curvature. Potential visual acuity Estimation of the visual acuity
(PVA) considering cornea as the only
Elevation map factor limiting vision.
Corneal height or elevation is defined by the distance of
each point on the corneal surface from a reference plane. Asphericity • Described quantitatively by
Positive elevation measurement implies that the corneal the Q value.
surface falls above the reference plane and are interpreted • Q= 0 for a sphere
as warm colours whereas negative values indicate that the • Q<0 for prolate surface
corneal surface falls below the reference plane and are • Q>0 for oblate surface
represented as cool colours on the elevation maps. • Normal cornea is prolate
Analysis of Orbscan Quad map (Figure 1) (ie, becomes flatter toward the
1. Anterior float (Elevation best fit sphere)– The anterior periphery) and has Q value of
-0.26.
best fit sphere (BFS) is calculated to best match the
anterior corneal surface. The elevation BFS map 4. Thickness (pachymetry) map– The pachymetry map
subtracts the calculated BFS against the eye surface in demonstrates the corneal thickness through the entire
millimeters. The difference between the sphere and cornea as well as the thinnest point of the cornea.
eye surface is expressed in radial distance from the Warm colours indicate thinner cornea while cooler
centre of the sphere. Green is “sea level” (match with a colours indicate thicker corneas.
sphere that best matches the cornea). Warmer colours
are above sea-level,while cooler colours are below sea 5. Anterior Chamber Depth and Anterior Iris–Lens
level. Surface - When measuring mean anterior chamber
2. Posterior float (Elevation best fit sphere) map– It depth (ACD) in phakic and pseudophakic eyes,
describes the back surface of the cornea in the same Orbscan correlates well with US A-scan and has greater
manner as the anterior float but using posterior corneal repeatability8-10.
measurements.
3. Keratometric (mean power) map– The keratometric Scheimpflug imaging
map displays the refractive power of the anterior The Pentacam (Oculus Inc., Washington) obtains images
surface of the cornea and translates anterior curvature of the anterior segment by a rotating Scheimpflug camera
into corneal power. which is a digital CCD (Charged coupled device) camera
with synchronous pixel sampling. The light source consists
of UV-free blue LED’s (wavelength 475 nm). Imaging is
based on the Scheimpflug principle, which occurs when
a planar subject is not parallel to the image plane. With

50 l DOS Times - Vol. 19, No. 4 October, 2013

Diagnostics

Figure 1: Analysis of orbscan Figure 2: Keratoconus

a rotating Scheimpflug camera, the Pentacam can obtain Figure 3: Pellucid marginal Degeneration
50 Scheimpflug images in less than 2 seconds. Each image
has 500 true elevation points, thus a total of 25,000 true Figure 4: Evaluation of patients post LASIK
elevation points are measured. The software utilizes a ray www. dosonline.org l 51
tracing algorithm to construct and calculate the anterior
segment. The device has two cameras, one on the centre for
controlling fixation and one mounted on a rotating wheel
for capturing slit images11, thus the center of the cornea can
be measured precisely.
Belin/Ambrosio enhanced ectasia display12 - A feature of the
pentacam HR, it is the first screening tool which represents
height data of the anterior and posterior corneal surface
in combination with a progression analysis of the corneal
thickness. It is overall more precise and enables early
keratoconus detection. The corneal thickness progression
analysis is calculated using concentric rings, starting at the
thinnest point and extending to the periphery (Table 3).
Advantages of Pentacam–
(1) Takes 50 meridional sections through the center of the

cornea which allows the system to realign the central
thinnest point of each section before it reconstructs the
corneal image. Thus it eliminates any eye movement
occuring during the examination and enables high
resolution imaging of the central cornea which is not
possible with other devices.
(2) Enables measurement of corneas with severe
irregularities, such as keratoconus, that may not be
amenable to Placido imaging.
(3) Enables calculation of pachymetry from limbus to
limbus.
(4) The Pentacam can provide corneal wavefront analysis
to detect higher-order aberrations.

Diagnostics

Table 3: Components of various models of pentacam

Pentacam Basic Pentacam Classic Pentacam HR

Qualitative assessment of the All features of basic plus Sharp Scheimpflug images for precise
cornea representation of implants, corneal rings, opacities
for lens and cornea.

Glaucoma screening: Software package-Refractive Precise imaging for determining positions of pIOLs
Pachymetry‑based IOP Calculation of corneal thickness and IOLs in reference to centering and tilting.
correction, chamber angle, progression for early keratoconus
volume and depth detection

Topography based Software package- Cataract Optional 3D pIOL simulation software including
keratoconus detection and Comprehensive cataract analysis aging prediction
classification (3D densitometry) and PNS
(Pentacam nucleus Staging)

Basic model can be upgraded Zernike analysis and corneal Contact lens fitting
to classic by including Wavefront e.g. for the selection of
additional optional software aspheric IOLs and determination of
modules. higher order aberrations

Belin/Ambrosio Enhanced Ectasia

Holladay Report and Holladay EKR (Equivalent
Keratometer Readings) for optimized
IOL‑calculation in post‑refractive patient eyes.

Clinical applications of corneal topography- • >+16mm (8 mm zone BFS)
Diagnosis of corneal ectatic disorders 2. Pellucid Marginal degeneration
1. Keratoconus • Zone of inferior corneal thinning within 2 to 3 mm of
Rabinowittz and Mcdonnell13,14 criteria –
• Central corneal power of greater than 47.2 D the inferior limbus.
• Inferior - Superior asymmetry value - 1.4D - 1.9D is • “Butterfly” appearance on topography- demonstrating

suggestive and >1.9D diagnostic. large amounts of against-the-rule astigmatism and
• Keratoconus predictability index (KPI)15,16- inferior corneal steepening (Figure 3).

derived by analysis of eight topographic indices Evaluation of patients post refractive surgery-
that represent specific topographic features of • After RK, topography demonstrates corneal
keratoconus. A KPI value > 0.23 is indicative of
keratoconus. flattening,greatest at the center and decreased at the
• KISA% index – Derived from product of four periphery (Figure 4,5).
indices: central K reading, I-S value, astigmatism • Helps to identify the surgical effect,postoperative
as measured by simK reading and skewed radial regression, decentered zones and treat central islands.
axis index (SRAX) (Figure 2). • To determine the refractive power change after surgery,
• 60% to 100% -is suspect and 100% - diagnostic. induced cylindrical change, and the temporal change
• Posterior float elevation- >40 µm17 suggestive of (healing effect) after PRK.
posterior ectasia. • Planning of astigmatism reducing incisions (LRI).
• Pentacam18
• Ant. elevation map difference >+15µm (9mm Cataract surgery
zone BFS) IOL power calculation in patients with previous refractive
• >+8µm (8 mm zone BFS) surgery- Corneal topography is utilized to determine the
• Post. elevation map difference >+20µm (9 “simulated keratometry” by analyzing the refractive power
of the central cornea19,20.
mm zone BFS)
Post penetrating keratoplasty
To guide selective suture removal, decide the placement of
arcuate incisions and compression sutures to reduce high
astigmatism21.

52 l DOS Times - Vol. 19, No. 4 October, 2013

Diagnostics

Figure 5: Corneal topography post -RK 8. Auffarth GU, Tetz MR, Biazid Y, Vo¨lcker HE. Measuring anterior
chamber depth with Orbscan Topography System. J Cataract Refract
Contact lens fitting Surg 1997; 23:1351–1355.
Fitting of rigid gas permeable lenses in keratoconus
patients22, post-RK patients and to compare with the 9. Vetrugno M, Cardascia N, Cardia L. Anterior chamber depth
manufacturer’s fitting nomogram for fitting aspheric rigid measured by two methods in myopic and hyperopic phakic IOL
gas permeable lenses23. implant. Br J Ophthalmol. 2000; 84: 1113–1116.
References
10. Koranyi G, Lydahl E, Norrby S, Taube M. Anterior chamber depth
1. Wilson SE, Klyce SD. Screening for corneal topographic abnormalities measurement: A-scan versus optical methods. J Cataract Refract
before refractive surgery. Ophthalmology 1994;101:147–52. Surg. 2002; 28:243–247.

2. Belin MW, Khachikian SS. An introduction to understanding 11. Satinder Pal S. Grewal, Evaluation of Anterior Segment pathologies
elevation-based topography: how elevation data are displayed - a using Pentacam, Highlights of Ophthalmology,2008,Vol 36 (1);17-
review. Clin Experiment Ophthalmol. 2009, 37(1):14 -29. 20.

3. Litoff D, Belin MW, Wynn SS, Smith RS. PAR technology corneal 12. Renato Ambrosio .Simplifying Ectasia Screening with Pentacam
topography system. Invest Ophthalmol. Vis Sci. 1991; 32 (4 Suppl): Corneal Tomography; Highlights of Ophthalmology Journal, Volume
922S. 38, No. 3, 2010.

4. Belin MW, Cambier JL, Nabors JR, Ratliff CD. PAR Corneal 13. Rabinowitz YS, Nesburn AB, McDonnell PJ. Videokeratography
Topography System (PAR CTS): the clinical application of close- of the fellow eye in unilateral keratoconus. Ophthalmology
range photogrammetry. Optom Vis Sci. 1995;72:828–37. 1993;100:181– 6.

5. Cairns G, McGhee CN. Orbscan computerized topography: 14. Rabinowitz YS, McDonnell PJ. Computer-assisted corneal
Attributes, applications, and limitations. J Cataract Refract Surg. topography in keratoconus. Refract Corneal Surg 1989;5:400–8.
2005; 31:205–220.
15. Maeda N, Klyce SD, Smolek MK, Thompson HW. Automated
6. American Academy of Ophthalmology. Corneal topography; keratoconus screening with corneal topography analysis. Invest
Ophthalmology Volume 106, Issue 8 , Pages 1628-1638, 1 August Ophthalmol Vis Sci 1994;35:2749-57.
1999.
16. Wilson SE, Lin DTC, Klyce SD. Corneal topography of keratoconus.
7. Smolin and Thoft’s The Cornea: Scientific Foundations and Clinical Cornea 1991;10:2– 8.
Practice,4th Edition.69:1121-1128.
17. Rao SN, Raviv T, Majmudar PA & Epstein RJ: Role of Orbscan II
in screening keratoconus suspects before refractive corneal surgery.
Ophthalmology 2002, 109: 1642–1646.

18. Jack T Holladay, Detecting Forme frustae Keratoconus with the
Pentacam, J Cataract Refractive Surgery 2008 (Sup): 11- 12.

19. Celikkol L, Pavlopoulos G, Weinstein B, et al. Calculation of
intraocular lens power after radial keratotomy with computerized
videokeratography. Am J Ophthalmol. 1995;120:739-50.

20. Alimisi S, Miltsakakis D, Klyce S. Corneal topography for intraocular
lens power calculations. J Refract Surg. 1996;12:S309–11.

21. Koffler BH, Smith VM. Corneal topography, arcuate keratotomy, and
compression sutures for astigmatism after penetrating keratoplasty. J
Refract Surg. 1996;12:S306 –9.

22. Rabinowitz YS, Garbus JJ, Garbus C, McDonnell PJ. Contact
lens selection for keratoconus using a computer-assisted
videophotokeratoscope. CLAO J. 1991;17:88 –93.

23. Wasserman D, Itzkowitz J, Kamenar T, Asbell PA. Corneal
topographic data: its use in fitting aspheric contact lenses. CLAO J.
1992;18:83–5.

www. dosonline.org l 53

Ophthalmic Lens MiscMeilslcaelnlaenoeouuss
Dispensing
Ashima Bhargava

B. Optom

Ashima Bhargava B. Optom, Pooja Singh B. Optom

Contact Lens Service, Rajendra Prasad Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences, New Delhi

The idea of eyewear was first conceived sometime near of two departments, surfacing or finishing, depending on
the end of the thirteenth century. At first, very few the type of lenses selected to complete the order.
people wore eyewear. The eyewear was rather strange Semi-finished lenses must first go through the surfacing
looking and was viewed with suspicion by many. department to have the back surfaces ground before being
The 1900s saw huge advancements in lens materials and sent to the finishing department. Finished lenses go through
designs and in frame styles and materials. In the early 1900s the finish department only because both sides of the lenses
corrected curve lenses were introduced that provided far are already ground (Table 1).
better vision than previous lenses. Further processing takes place of lens blanks and finished
As we can see, the optical industry has been very active optical lenses are obtained. It is carried out in following
during the last hundred years and the trend to continue steps.
bringing out innovative products and technology shows no
indication of slowing1. Table 1: Lenses finishing
“Ophthalmic dispensing’’ means the design, verification,
and delivery to the intended wearer of lenses, frames, Process Procedure Example
and other specially fabricated optical devices upon Casting
prescription. It includes, but is not limited to, prescription Where a finished or semi- CR39 casting
analysis and interpretation; the taking of measurements Moulding finished lens is produced
to determine the size, shape, and specifications of the from raw chemicals using
spectacle lenses, frames, or lens forms best suited to the Multi part a chemical process
wearer’s needs; the preparation and delivery of work systems
orders to laboratory technicians engaged in grinding lenses Surfacing Where the lens material Polycarbonate
and fabricating eyewear; the verification of the quality of exists and it is reshaped
finished ophthalmic products, the adjustment of lenses or by pressure and heat
frames to the intended wearer’s face and the adjustment, into the finished or semi-
replacement, and reproduction of previously prepared finished lens form
ophthalmic lenses, frames.
The optical laboratory plays a major part in the ever- Such as laminating and Fused glass
changing field of vision. Today’s optical laboratory services fusing, where two or bifocals
go beyond just making lenses. The lenses and frames more pieces are joined to
are picked from the stock or they are ordered from the form the final lens
manufacturers.
The order then enters the processing part of the lab in one The lens materials already Rx surfacing
exist and cutting and/or
grinding and polishing
is used to create the lens
form

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Table 2: Different materials available for spectacle lenses • Smoothing - done to true the curve and to produce
a surface capable of taking a good polish.
Material R e f r a c t i v e ABBE Reflectance**
Index value* • Polishing-to obtain good polished surface. Rouge(iron
oxide) also known as cerium oxide is attached to a soft
CR-39 1.50 58 4.0 pad to polish lens surface.

Polycar- 1.58 29 5.2 • Deblocking and cleaning-after completion of the
bonate process lens is separated from its holder either by
immersing in cold water, tapping the blank with
Trivex 1.53 46 4.4 wooden mallet etc and cleaned properly.

Crown glass 1.52 59 4.3 The process is repeated for other surface of the lens.
Advantages and disadvantages of different lens
1.60(HI)*** 1.60 42 5.3 The eye care professional can look at the characteristics
of the available materials and decide which is the best to
1.70(HI) 1.71 35 6.7 recommend for the patient’s needs. Lens materials can be
differentiated by their weight, thickness, transmission of
1.80(HI) 1.81 25 8.2 radiant energy and optical performance (Table 2,3,4).
Types of lenses on the basis of viewing zones
* ABBE Value- It is inversely proportional to the chromatic Basic lens styles are designed by the manufacturer to meet
aberrations induced as light passes through it the vision needs of the patient. The final lens selection
process should take into consideration the style, design,
** Reflectance- The percentage of light reflected from a highly lens material and enhancements.
polished surface of that material and is calculated from the Single-vision lenses
refractive index of material The single-vision lens provides vision correction for one
viewing area. The corrected area can be for far distance,
*** HI- High index near distance or reading. The lens power for the distance

• Marking - to correctly locate the lens
• Blocking - to hold the lens firmly and accurately
• Grinding –
• Roughing- generating desired curvature by

removing greater part of unwanted material.
• Trueing- grounding blank on the proper tool as

required by specific power.

Table 3: Lens Materials

Lens Material Advantages Disadvantages

Glass lenses Superior optics Can’t be tinted
Stable material Not impact resistant (most brittle)
Scratch resistant Heavy

CR-39 m Lighter than glass lenses Susceptible to scratching(correctable by coatings)
Readily tintable Less suitable for high powered prescriptions due to
Less likely to fog lower refractive index

Polycarbonate Highly impact resistant Poor optical quality
Inherent UV protection Susceptible to scratching(correctable by coatings)
Susceptible to stress fractures in drill mounts
Not readily tintable

High index Thinner and lighter than glass and plastic Susceptible to scratching (correctable by coatings)
lenses Susceptible to backside and inner surface
Better optical quality than polycarbonate reflections(correctable with Anti-Reflection coating
i.e. ARC)

Trivex Impact resistant as polycarbonate Susceptible to scratching(correctable by coatings)
Better optical quality than polycarbonate
Tintable
Lightest lens material available
Inherent UV protection
High tensile strength

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Table 4: Absorptive tints and protective coatings

Type Purpose Application Advantages Disadvantages

Tints To filter out a • Light tints- indoor • Protection from harmful • In dark tinted lenses
portion of the work, albinism, cosmetic or troublesome rays (of without added UV
transmitted light purpose etc visible spectrum, infrared protection may cause
• Dark tints- aphakia, and ultraviolet rays) more damage to the
photophobia, outdoor • Increased visual comfort eyes
works, driving during day • Dark tints may
time sometime reduce
vision e.g. in albinism

Photochromic Can adapt • To enhance the vision • Convenience • May not return
to lighting of patients who have • Adapts to any current to completely
conditions. In various eye pathologies, lighting conditions transparent state if
sunlight, lens including macular the room is specially
darkens and degeneration bright
indoors, they • Who have a lot of work • May not always
lighten to look like get as dark as regular
regular eye wear sunglasses
• May take several
minutes to go from
light to dark and dark
to light

ARC (anti To reduce • Normal prescriptions • Improves vision by • Unstable at high
reflective reflections from and bifocals to avoid eliminating reflections temperature
coating) lens surface ghost images • Improves night vision. • Very prone to
• Improve cosmesis • Reduces glare from head scratches
in high myopic, lights, street lamps, rain
anisometropic slick surfaces etc while
corrections etc driving
• High index lenses • Renders lenses invisible.
Cosmetically better

Anti scratch To reduce lens • Mostly used in plastic Better vision through • Not permanent
coating surface scratching lenses scratch free lens

Polaroid lenses Allows • Snowscreen (skiers) • Eliminates glare • Expensive
transmission of • Seascreen (water, • Enhances visual acuity
light in one plane fishermen and boaters) • Enhances colour contrast
• Landscreen (driving,
hunting, golfing etc)

*Lately, some other coatings have been developed like OPTIFOG and HYDROPHOBIC which resist fog and water on the lens surface

correction will be minus while the correction for near • Astigmatism Power Prescription
distance and reading will be plus power. The prescription • +1.00 - 0.50 x 90
can be written for spherical correction, with the same Bifocals
power in all directions, or for correcting astigmatism with Bifocal lenses are designed with two different viewing
a spherical correction combined with a cylinder power areas, one for distance and one for near viewing. The
amount to create two lens powers 90 degrees apart at a distance area is designed like a single-vision lens, while
specified axis (Table 5). the near area contains the distance prescription and the
Example: additional amount of plus spherical power needed to see
• Sphere Power Prescription at a reading distance of approximately 19 inches. The
• + 1.00 sphere additional amount of plus power (also called the add
power), for reading is located in an area referred to as the

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Table 5: Types of lenses on the basis of design- Lens designers design lenses to provide the best visual performance, cosmetic
appearance, and comfort. Proper lens selection, correct facial measurements, and correct frame alignment are all necessary to
maintain the design intent

Type Applications Advantages Disadvantages

Single cut meniscus lens • Moderate degree • Cosmetically better • Can’t be used for high
of refractive errors myopic or hyperopic
correction

Lenticular-central portion of lens is • Aphakia • Less weight • Cosmetically poor
ground to have aperture. Peripheral • High hyperopia • Lesser peripheral prismatic • Smaller field of view
part of lens acts as carrier • High myopia effect

Aspheric - made by modifying the • Aphakia • Better optics • Expensive than
lens curvature peripherally (Figure 1) • High hyperopia • Lesser aberrations conventional lenses
• Thinnest, lightest and
flattest lens profile
• Increased field of view
• Better peripheral vision

segment or seg. Segment shapes can be round, straight top, Table 6 Advantages Disadvantages
or a straight line across the lower half of the lens [(Executive Type of bifocal • Nearly visible, • Though nearly
or Franklin), (Figure 1), (Table 6)]. Straight top/ cosmetically visible, presence
flat top/ D style attractive of dividing line is
Progressive addition lenses (PALS) bifocal • Good sized obvious
Progressive lenses are sometimes called no-line, invisible field of view • Reading area
or PAL (Progressive Additive Lens). They are designed with Round segment is some what
no lines to allow the presbyopic patient to see at distance, bifocal/ kryptok • Nearly visible, reduced
intermediate and near. The front surface of the lens changes cosmetically • Image jump is
from distance to near in curvature to create the additional Executive/ attractive; even present
power needed for near viewing with no interruption in franklin/bifield/ more than • Greater
vision from the top to the bottom of the lens. dualens Bifocals straight top excursion of eye
bifocals is required into
Today’s progressive lenses are increasing in popularity • Has big field of widest part of the
as the lens of choice for the presbyope. Presbyopes are view bifocals
changing from their line-style multifocals to progressive • Less image • Heavy
lenses to enjoy the benefits of no lines and continuous jump • Ugly
vision from far to near (Figure 2).
• Improved annoyance-free vision
Progressive lenses are identified by finding the manufacturer- • Long term trouble free use
engraved circles to locate the add power and manufacturer
logo. The viewing areas can also be marked once the Disadvantages-
engraved circles are identified. • Expensive
• Takes time to get properly adapted
Features- • Peripheral vision is reduced
• Most advanced presbyopic lenses
• Cosmetically better Office Environment Lens
• Correct for all distances Many patients work in an office environment that restricts
• Smooth transition from one correction to the other their vision to intermediate and near viewing. The time
• No image jump or displacement spent in this environment can be for a few hours to all day
Advantages -
• Youthful look
• Improved visual performance at distance, intermediate,

near
• Easy uninterrupted visual comfort

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Figure 1 Frame Selection for Cosmetics and Fit
Frames are designed in different styles for fit and cosmetic
Figure 2 appeal. Each frame consists of the front, which has two
eyewires (right and left eye) and the bridge area, which
so special lenses, commonly called computer lenses, are rests on the nose. Attached to the front are two temples,
designed to meet the vision needs of patients working in which are available in different styles. The attachment area
an office environment. The lenses can be single vision, of the front and temple is often called the endpiece.
bifocals, trifocals or progressive. The power prescribed in Full Frames
the prescription is for intermediate and near use. Full frames consist of two eyewires that go around the
Segment lenses are available in different sizes and entire circumference of the lens. These are made of metal,
intermediate powers. They are also available in progressive plastics or a combination of materials.
lenses, which gradually change in power from intermediate Drilled Rimless Frames
to reading with no lines. The use of tints, UV blocking and The lenses in a rimless frame are held in place with bridge
anti-reflection coating should be recommended to enhance and endpiece mountings. The lenses are attached to the
the performance of the lens. mounting with screws through holes drilled in the lenses.
Spectacle frame materials- This type of frame is sometimes called a three-piece
Frame Materials mounting. Be careful when adjusting this frame to avoid
Today’s frames are made of many different types of materials lens breakage. Rimless lenses should be braced at the point
depending on the required style, durability, color, and ease of attachment to the lens before adjusting. Special hand
of use. For the most part, though, frames are made from tools are available to help accomplish this.
plastic and metal. Grooved Rimless Frame
Plastic frames are available in many colors and are usually A partial eyewire extends around a semi-rimless frame,
thicker and wider than metal frames. Metal frames tend to holding the lens in place with a nylon string around the
be thinner, lighter-weight, and more durable. Each material circumference of the lens. The lens edge is grooved to hold
has features that make it popular. the nylon string in place.
Combination Frame
Combination frames combine a metal chassis to hold the
lens, two trim endpieces attached to the chassis and two
temples attached to the endpieces. The endpieces and
temples can be plastic or metal.
Half-Eye Frame
The lens area for a half-eye frame is designed with a small
reading lens to allow the patient to look over the frame top
for distance viewing.
Sports Frames
Specifically designed for sports activities, these frames can
be made from different materials and should have high
impact resistant lenses for maximum protection
Lens Enhancements
Scratch Resistant Treatment (S/R)
When plastic lenses emerged in the ‘70s as a major lens
material, one disadvantage was their soft surface, which
scratched easier than glass lenses. Since then, a scratch-
resistant treatment has been developed for use on plastic
lenses that significantly reduces scratching.

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Even with a scratch-resistant (S/R) treatment on their lenses, Polarized sun lenses have a special filter designed to block
patients should always be told that no material is scratch that reflective glare. The benefits of polarized lenses can
proof. All lenses can be scratched, even glass. be shown using demonstration units or polarized lens
Today’s S/R treatments are better than ever. They are samples. When patients see the benefit of these lenses
durable and have excellent adhesion to the lens surface. they almost never go back to regular sun lenses. Today’s
For some lens styles a super-hard S/R treatment is available polarized lenses are available in a variety of materials.
but these lenses cannot be tinted. Edge Treatments
Anti-Reflection Treatment (A/R) There are various treatments that can be applied to the
Eight percent of light is lost as it passes through a clear glass edges of a lens to improve cosmetics and performance,
or plastic lens. The percentage of loss actually increases especially for rimless edges. Polished edge treatments give
with high index material to as much as 12 to 16%. Where an elegant look to the lens. Rolling the edge can reduce
does the light go? edge thickness and can be combined with a polished edge
The reduction of light transmission is due to both external treatment. High minus power lenses in a full eyewire frame
and internal reflections that occur as light passes through can be color coated to blend with the frame color and
the lens. External reflections are annoying to the patient reduce reflections through the edge thickness
and are not cosmetically pleasing. From the front side, Facial Measurements
external reflections have a mirror effect, which hides the Knowing the correct powers for each lens is not enough to
eyes and is noticeable to others. ensure vision correction. The lenses also must be aligned
Patients also complain about back surface reflection when properly in front of the eyes and the frame holding the lenses
they mention “seeing their eyes” or seeing side reflections also must be comfortable to the patient. It is important to
off the back lens surface. Internal reflections can create have the correct facial measurements to properly align the
secondary images of objects. This is especially noticeable eyewear.
when looking at bright lights in the dark. Anti-reflection PD Measurements
treatment reduce these reflections. The distance from the center of the pupil in the right eye to
Ultraviolet Protection (UV) Treatment the center of the pupil in the left eye is called the pupillary
Most consumers are aware of the harmful effects of long- distance, or PD for short. This measurement can be taken
term exposure to ultraviolet radiation (sun exposure) on for distance viewing when the lines of sight for the eyes
the skin, but some people may be unaware that eyes also are parallel looking at a distant object (Far PD), and can
need protection from the sun. Regular glass or plastic also be taken for reading at near distance (Near PD). The
lenses must be treated to provide UV protection. Plastic near PD measurement will be shorter than the distance PD
lenses can be dip-coated, and glass lenses color-coated, measurement by 2 to 5mm because the eyes turn in, or
to provide UV protection. Most mid- and all high-index converge, at near distance.
materials provide protection due to the chemistry of the Vertical Height Measurements
lens material. Photochromic lenses also provide protection. Vertical height measurements are taken to determine
Photochromic lenses darken when exposed to UV radiation bifocal, trifocal, or progressive height. This measurement is
(sunlight) and lighten in its absence. They are available in taken from the lowest part of the eyewire to the guideline.
glass and plastic. The two most popular colors are gray and The guideline for a bifocal is the lower lid, for a trifocal it
brown but additional colors are available from some lens is the lower edge of the pupil, and for progressive addition
manufacturers. lenses it is the center of the pupil.
Information is available from the manufacturer detailing Depending on specific circumstances, the final vertical
how light or dark photochromic lenses change, the rate height measurement might be more, less, or the same as
of change and what external factors (such as temperature) the guideline measurements. Factors that may affect the
can affect performance. Patients should be informed that final vertical height measurements are:
photochromic lenses do not turn to their darkest shade 1. The amount of use at the near viewing area
behind a windshield. 2. The customer’s posture
Polarized Sun Lenses 3. The pantoscopic angle
Polarized sun lenses have an important advantage over 4. How far the lenses will set from the face
regular sunglasses. They block reflective glare where regular 5. The prescription
sunglasses do not. For example, light reflected off a surface
like water or the hood of a car is bright and annoying.

60 l DOS Times - Vol. 19, No. 4 October, 2013